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伊藤 由起イトウ ユキ

所属部署医学研究科環境労働衛生学分野
職名准教授
メールアドレス
ホームページURLhttp://www.med.nagoya-cu.ac.jp/hygiene.dir/
生年月日
Last Updated :2020/06/02

研究者基本情報

学位

  • 博士(医学)

所属学協会

  • 日本衛生学会
  • 日本産業衛生学会
  • 国際疫学会
  • 日本疫学会
  • 日本毒性学会
  • 日本毒性病理学会
  • 環境ホルモン学会

研究活動情報

研究分野

  • ライフサイエンス, 衛生学、公衆衛生学分野:実験系を含まない
  • ライフサイエンス, 衛生学、公衆衛生学分野:実験系を含む
  • ライフサイエンス, 衛生学、公衆衛生学分野:実験系を含まない
  • ライフサイエンス, 衛生学、公衆衛生学分野:実験系を含む
  • 環境・農学, 化学物質影響
  • 環境・農学, 放射線影響
  • 環境・農学, 環境影響評価
  • ライフサイエンス, 医療管理学、医療系社会学

研究キーワード

    リスク評価, 環境化学物質, 毒性学, 衛生学

論文

  • Biomonitoring Method for Neonicotinoid Insecticides in Urine in Non-toilet-trained Children Using LC-MS/MS., Ueyama J, Aoi A, Ueda Y, Oya N, Sugiura Y, Ito Y, Ebara T, Kamijima M, Food Additives & Contaminants: Part A, in press,   2020年, 査読有り
  • Exposure levels of organophosphate pesticides in Japanese diapered children: contributions of exposure-related behaviors and mothers’ considerations of food selection and preparation, Oya N, Ito Y, Ebara T, Kato S, Hioki K, Aoi A, Ueyama J, Oguri T, Shoji N, Sugiura-Ogasawara M, Saitoh S, Kamijima M, Environment International, 134, 105294 - 105294,   2020年01月, 査読有り
  • Organophosphate Agent Induces ADHD-Like Behaviors via Inhibition of Brain Endocannabinoid-Hydrolyzing Enzyme(s) in Adolescent Male Rats, Ito Y, Tomizawa M, Suzuki K, Shirakawa Y, Ono H, Adachi K, Suzuki H, Shimomura K, Nabeshima T, Kamijima M, J. Agric. Food Chem, 68, 2547 - 2553,   2020年01月, 査読有り
  • Within-individual and interlaboratory variability analyses of urinary metabolites measurements of organophosphorus insecticides, Ito Y, Ueyama J, Nakayama SF, Isobe T, Oya N, Sato H, Ebara T, Yoshimasu K, Tsuno K, Tatsuta N, Nakai K, Kamijima M, Journal of Exposure Science and Environmental Epidemiology, in press,   2020年, 査読有り
  • Occupational exposure limits for cumene, 2,4-dichlorophenoxy acetic acid, silicon carbide whisker, benzyl alcohol, and methylamine, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications, Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Koji Harada, Hajime Hori, Seichi Horie, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakumu, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano, Journal of Occupational Health, 61, (4) 328 - 330,   2019年07月, 査読有り
  • Comprehensive review of 2-ethyl-1-hexanol as an indoor air pollutant., Wakayama T, Ito Y, Sakai K, Miyake M, Shibata E, Ohno H, Kamijima M, Journal of Occupational Health, 61, 19 - 35,   2019年, 査読有り
  • Cohort profile: Aichi regional sub-cohort of the Japan Environment and Children’s Study (JECS-A), Ebara T, Yamada Y, Shoji N, Ito Y, Nakagawa A, Miyachi T, Ozaki Y, Omori T, Suzuki S, Kojima M, Ueyama J, Tomizawa M, Kato S, Oguri T, Matsuki T, Sato H, Oya N, Sugiura-Ogasawara M, Saitoh S, Kamijima M, BMJ Open, 9,   2019年, 査読有り
  • Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: a review., Ito Y, Kamijima M, Nakajima T, Environmental Health and Preventive Medicine, 24,   2019年, 査読有り
  • Simple method to detect triclofos and its metabolites in plasma of children by combined use of liquid chromatography tandem-mass spectrometry and gas chromatography-mass spectrometry., Sato H, Ito Y, Inoue M, Nakahira Y, Hashimoto S, Nakajima T, Kamijima M, Scientific Reports, 9,   2019年, 査読有り
  • In utero exposure to di(2-ethylhexyl)phthalate suppresses blood glucose and leptin levels in the offspring of wild-type mice., Hayashi Y, Ito Y, Naito H, Tamada H, Yamagishi N, Kondo T, Ishikawa T, Gonzalez FJ, Nakajima T, Toxicology, 415, 49 - 55,   2019年, 査読有り
  • Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan, Hioki K, Ito Y, Oya N, Nakayama SF, Isobe T, Ebara T, Shibata K, Nishikawa N, Nakai K, Kamida T, Ueyama J, Sugiura-Ogasawara M, Kamijima M, Environmental Health and Preventive Medicine, 24,   2019年, 査読有り
  • Occupational Exposure Limits for ethylidene norbornene, ethyleneimine, benomyl, and 2,3-epoxypropyl methacrylate, and classifications on carcinogenicity., Atsuko Araki, Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Hajime Hori, Seichi Horie, Hyogo Horiguchi, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Tatsuya Ishitake, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Takeyasu Kakumu, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Makiko Nakano, Tetsuo Nomiyama, Hirokazu Okuda, Masayuki Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Kenya Yamamoto, Yuko Yamano, Takenori Yamauchi, Eiji Yano, Journal of occupational health, 60, (4) 333 - 335,   2018年07月25日, 査読有り
  • Epididymal phospholipidosis is a possible mechanism for spermatotoxicity induced by the organophosphorus insecticide fenitrothion in rats., Miyake M, Ito Y, Suzuki H, Tomizawa M, Sato H, Liu M, Okamura A, Nakajima T, Ohtani K, Takino H, Inagaki H, Kamijima M, Toxicology letters, 285, 27 - 33,   2018年, 査読有り
  • Exposure reconstruction of trichloroethylene among patients with occupational trichloroethylene hypersensitivity syndrome., Nakajima T, Wang H, Ito Y, Naito H, Wang D, Zhao N, Li H, Qiu X, Xia L, Chen J, Wu Q, Li L, Huang H, Kamijima M, Industrial health, 56, (4) 300 - 307,   2018年, 査読有り
  • 幼児向けADHD関連行動評価尺度「行動特徴のチェックリスト(BCL)」の妥当性と信頼性の検討, 津野香奈美, 吉益光一, 林隆, 龍田希, 伊藤由起, 上島通浩, 仲井邦彦, 日本衛生学会誌, 73, 225 - 234,   2018年, 査読有り
  • Occupational exposure limits for ethylene glycol monobutyl ether, isoprene, isopropyl acetate and propyleneimine, and classifications on carcinogenicity, occupational sensitizer and reproductive toxicant., Kenichi Azuma, Ginji Endo, Yoko Endo, Tetsuhito Fukushima, Kunio Hara, Hajime Hori, Seichi Horie, Hyogo Horiguchi, Masayoshi Ichiba, Gaku Ichihara, Masayuki Ikeda, Tatsuya Ishitake, Akiyoshi Ito, Yuki Ito, Satoko Iwasawa, Michihiro Kamijima, Kanae Karita, Takahiko Katoh, Toshio Kawai, Toshihiro Kawamoto, Reiko Kishi, Shinji Kumagai, Yukinori Kusaka, Akiko Matsumoto, Muneyuki Miyagawa, Hiroyuki Miyauchi, Yasuo Morimoto, Kasuke Nagano, Hisao Naito, Tamie Nakajima, Tetsuo Nomiyama, Hirokazu Okuda, Kazuyuki Omae, Haruhiko Sakurai, Kazuhiro Sato, Tomotaka Sobue, Yasushi Suwazono, Toru Takebayashi, Tatsuya Takeshita, Akito Takeuchi, Ayano Takeuchi, Masatoshi Tanaka, Shigeru Tanaka, Teruomi Tsukahara, Masashi Tsunoda, Susumu Ueno, Jun Ueyama, Yumi Umeda, Yuko Yamano, Takenori Yamauchi, Eiji Yano, Journal of occupational health, 59, (4) 364 - 366,   2017年07月27日, 査読有り
  • Quantitative analysis of organophosphate insecticide metabolites in urine extracted from disposable diapers of toddlers in Japan, Naoko Oya, Yuki Ito, Keisuke Hioki, Yuya Asai, Arisa Aoi, Yuka Sugiura, Jun Ueyama, Tomoko Oguri, Sayaka Kato, Takeshi Ebara, Michihiro Kamijima, INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH, 220, (2) 209 - 216,   2017年03月, 査読有り, Background and aim: Epidemiological studies linking insecticide exposure to childhood neurodevelopment have been gaining global attention. Despite the rapid development of the central nervous system in early childhood, studies regarding the biological monitoring of insecticide exposure in diapered children are limited. In this study, we aimed to clarify the concentrations of organophosphate (OP) insecticide metabolites in toddler urine extracted from disposable diapers in Japan. Methods: We recruited diapered children from the Aichi regional subcohort participants of the Japan Environment and Children's Study (JECS) at the time of their 18-month checkup. A total of 116 children wore designated disposable diapers overnight, which were then sent as refrigerated cargo. The urine was extracted from the diapers using acetone and analyzed by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) to determine the concentrations of six dialkyl phosphates (DAPs) (i.e., dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP], diethyl phosphate [DEP], diethyl thiophosphate [DETP], and diethyl dithiophosphate [DEDTP]). DAP absorption into the diapers was quantified to calculate the urinary DAP concentrations. Results: The DAP recovery using the developed method yielded between 54.2% (DEDTP) and 101.4% (DEP). Within-run precision expressed as the relative standard deviation was between 2.4% and 14.7%, and the between-run precision was between 3.1% and 8.5%. A Bland-Altman analysis confirmed the agreement between the results obtained by the developed method and by the measurements for the corresponding urine without diaper absorption. The geometric means (GM) of urinary DMP, DMTP, DMDTP, DEP, DETP, and total DAPs (EDAP) were 3.6, 3.9, 0.9, 6.0, 0.6 mu g/L, and 137.6 nmol/L, respectively. The GM of DEDTP was not calculated due to its low detection rate. Conclusions: We successfully established a method to measure the DAP concentrations in urine extracted from diapers and this is the first report of these pesticide concentrations in diapered children in Japan. (C) 2016 Elsevier GmbH. All rights reserved.
  • Organophosphorus insecticide dichlorvos inhibits fatty acid amide hydrolase in the male reproductive organs of rats., Oya N, Ito Y, Kamijima M, Fundam Toxicol Sci, 4, 201 - 205,   2017年, 査読有り
  • Determinants of polyunsaturated fatty acid concentrations in erythrocytes of pregnant Japanese women from a birth cohort study: study protocol and baseline findings of an adjunct study of the Japan environment & Children's study, Shoji Saito, Terue Kawabata, Nozomi Tatsuta, Fumiko Kimura, Teruo Miyazawa, Satoshi Mizuno, Hidekazu Nishigori, Takahiro Arima, Yasuo Kagawa, Kouichi Yoshimasu, Kanami Tsuno, Yuki Ito, Michihiro Kamijima, Kunihiko Nakai, Nobuo Yaegashi, ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE, 22, (1) ,   2017年, 査読有り, Background: N-3 polyunsaturated fatty acids (n-3 PUFA) may have multiple beneficial effects on the outcome of pregnancy, maternal health and child development. The present study introduced the protocol of a birth cohort study to examine the beneficial effects of n-3 PUFA status in pregnant Japanese women as an adjunct study of the Japan Environment and Children's Study (JECS). Methods: The JECS participants in the coastal areas of Miyagi Prefecture were further invited to participate in this adjunct study, and 1,878 pregnant women were enrolled prior to delivery. Their n-3 PUFA status was evaluated with fatty acid profiles in erythrocytes of maternal blood collected from 1,623 mothers at 24-30 weeks of gestation and cord blood from 1,505 deliveries. Results: The baseline results, including comprehensive data on the fatty acid status and determinants affecting the PUFA status, were analyzed. In stepwise multivariate analyses, the cord blood docosahexaenoic acid (DHA) level was found to be significantly influenced by the DHA level in maternal blood, the child's sex, and the gestational period. The maternal DHA level was influenced by fish intake, maternal age, and the prepregnancy body mass index. While cord blood eicosapentaenoic acid (EPA) was influenced by maternal EPA, fish intake, and season at birth, additional factors such as maternal education, household income, and smoking habits affected the maternal EPA content. Conclusion: Further studies are warranted to clarify the nutritional impacts of n-3 PUFA in pregnant Japanese women of the cohort study.
  • 小児におけるトリクロホスの投与量の最適化, 井上美帆, 佐藤博貴, 糸原光太郎, 加藤祐子, 石井祥代, 伊藤由起, 中平有紀, 那須民江, 上島通浩, 矢野育子, 松原和夫, 佐和貞治, 橋本悟, 臨床薬理の進歩, 38, 71 - 78,   2017年, 査読有り
  • Nanoparticle-Rich Diesel Exhaust-Induced Liver Damage via Inhibited Transactivation of Peroxisome Proliferator-Activated Receptor Alpha, Yuki Ito, Yukie Yanagiba, Doni Hikmat Ramdhan, Yumi Hayashi, Yufei Li, Akira K. Suzuki, Michihiro Kamijima, Tamie Nakajima, ENVIRONMENTAL TOXICOLOGY, 31, (12) 1985 - 1995,   2016年12月, 査読有り, Diesel exhaust emission contains a high amount of nano-sized particles and is considered to be systemically distributed in the body. However, few studies about the effects of nanoparticle rich-diesel exhaust (NR-DE) on liver have been reported. The present investigation focuses on the effects of NR-DE on livers in rats, especially concerning inflammation and lipid metabolism. Male F344 rats were exposed to fresh air or low (24+/-7 mu g/m(3)), medium (3+/-4 mu g/m(3)) and high (138+/-20 mu g/m(3)) concentrations of NR-DE for 1, 2, or 3 months (5 hours/day, 5 days/week). Exposure to both medium and high concentrations of NR-DE for one month increased plasma asparate aminotransferase and alanine aminotransferase activities, while only high concentrations increased plasma interleukin-6 and hepatic nuclear factor kappa B (NF kappa B), suggesting that activation of hepatic inflammatory signaling took place. Although these exposures elevated peroxisome proliferator-activated receptor (PPAR) alpha levels or its binding activity to the response element, neither activated PPAR alpha-target genes such as beta-oxidative enzymes nor inhibited NF kappa B elevation. Thus, NR-DE may contain some materials that inhibit PPARa activation in relation to lipid metabolism and inflammation. Taken together, NR-DE exposure at one month may cause inflammation; however, this finding may not be observed after a longer exposure period. (C) 2015 Wiley Periodicals, Inc.
  • Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium, Mio Miyake, Yuki Ito, Masato Sawada, Kiyoshi Sakai, Himiko Suzuki, Tatsuo Sakamoto, Kazunobu Sawamoto, Michihiro Kamijima, ARCHIVES OF TOXICOLOGY, 90, (8) 1949 - 1958,   2016年08月, 査読有り, The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at a parts per thousand yen20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H.
  • Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids, Aya Osaka, Jun Ueyama, Takaaki Kondo, Hiroshi Nomura, Yuka Sugiura, Isao Saito, Kunihiko Nakane, Ayuko Takaishi, Hiroko Ogi, Shinya Wakusawa, Yuki Ito, Michihiro Kamijima, ENVIRONMENTAL RESEARCH, 147, 89 - 96,   2016年05月, 査読有り, The use of neonicotinoid (NEO) insecticides has increased over the past decade not only in Japan but also worldwide, while organophosphate (OP) and pyrethroid (PYR) insecticides are still conventionally used in agriculture and domestic pest control. However, limited data are currently available on the NEO exposure levels, especially in children, who are particularly vulnerable to environmental toxicants. Thus, the purpose of this study was to characterize the exposure to NEOs, as well as OPs and PYRs, in three-year-old Japanese children by assessing the range, distribution, and seasonal differences of the urinary concentrations of seven NEOs (acetamiprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, imidacloprid, and nitenpyram); four OP metabolites (dialkylphosphates IDAPsp, including dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate; and three PYR metabolites (3-phenoxybenzoic acid, trans-chrysanthemumdicarboxylic acid, and 3-(2,2-dichloroviny1)-2,2- dimethylcyclopropane carboxylic acid). Urine samples were collected from 223 children (108 males and 115 females) in the summer and winter months. The detection rates of NEOs were 58% for dinotefuran, 25% for thiamethoxam, 21% for nitenpyram, and <16% for all other NE05. The median and maximum concentrations of the sum of the seven NEOs (NEO) were 4.7 and 370.2 nmol/g creatinine, respectively. Urinary Sigma NEO, dimethylphosphate, and all PYR metabolite concentrations were significantly higher in the summer than in the winter (p < 0.05). The creatinine-adjusted concentration of Sigma NEO significantly correlated with those of all DAPs (p < 0.05) but not with those of the PYR metabolites. Moreover, the NEO-detected group showed higher urinary EDAP (sum of four OP metabolites) concentrations than the group without NEO detection. These findings suggest that children in Japan are environmentally exposed to the three major insecticide lines, and that the daily exposure sources of NEOs are common to those of Ups. (C) 2016 Elsevier Inc. All rights reserved.
  • Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers, Hirotaka Sato, Yuki Ito, Jun Ueyama, Yuya Kano, Tomoya Arakawa, Masahiro Gotoh, Takaaki Kondo, Yuka Sugiura, Isao Saito, Eiji Shibata, Michihiro Kamijima, JOURNAL OF OCCUPATIONAL HEALTH, 58, (1) 56 - 65,   2016年01月, 査読有り, Objectives: Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present cross-sectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low-level OPs. Methods: Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 +/- 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos-methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography-mass spectrometry. Results: The maximum differences in enzyme activities between individuals were 64.6-, 6.3-, 7.7-, and 2.0-fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE. Conclusions: While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities.
  • Comparison of Different Urine Pretreatments for Biological Monitoring of Pyrethroid Insecticides., Toshima H, Yoshinaga J, Shiraishi H, Ito Y, Kamijima M, Ueyama J, Journal of Analytical Toxicology, 39, (2) 133 - 6,   2015年
  • Biological monitoring method for urinary neonicotinoid insecticides using LC-MS/MS and its application to Japanese adults., Ueyama J, Nomura H, Kondo T, Saito I, Ito Y, Osaka A, Kamijima M, J Occup Health, 56, (6) 461 - 8,   2015年
  • Prenatal Exposure to Di(2-ethylhexyl) phthalate and Subsequent Infant and Child Health Effects., Nakajima T, Hayashi Y, Ito Y, Food Safety, 3, (3) 70 - 83,   2015年, 査読有り, 招待有り
  • Fenitrothion action at the endocannabinoid system leading to spermatotoxicity in Wistar rats, Yuki Ito, Motohiro Tomizawa, Himiko Suzuki, Ai Okamura, Katsumi Ohtani, Mari Nunome, Yuki Noro, Dong Wang, Tamie Nakajima, Michihiro Kamijima, TOXICOLOGY AND APPLIED PHARMACOLOGY, 279, (3) 331 - 337,   2014年09月, Organophosphate (OP) compounds as anticholinesterase agents may secondarily act on diverse serine hydrolase targets, revealing unfavorable physiological effects including male reproductive toxicity. The present investigation proposes that fenitrothion (FNT, a major OP compound) acts on the endocannabinoid signaling system in male reproductive organs, thereby leading to spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) in rats. FNT oxon (bioactive metabolite of FNT) preferentially inhibited the fatty acid amide hydrolase (FAAH), an endocannabinoid anandamide (AEA) hydrolase, in the rat cellular membrane preparation from the testis in vitro. Subsequently, male Wistar rats were treated orally with 5 or 10 mg/kg FNT for 9 weeks and the subchronic exposure unambiguously deteriorated sperm motility and morphology. The activity-based protein profiling analysis with a phosphonofluoridate fluorescent probe revealed that FAAH was selectively inhibited among the FNT-treated cellular membrane proteome in testis. Intriguingly, testicular AEA (endogenous substrate of FAAH) levels were elevated along with the FAAH inhibition caused by the subchronic exposure. More importantly, linear regression analyses for the FNT-elicited spermatotoxicity reveal a good correlation between the testicular FAAH activity and morphological indices or sperm motility. Accordingly, the present study proposes that the FNT-elicited spermatotoxicity appears to be related to inhibition of FAAH leading to over-stimulation of the endocannabinoid signaling system, which plays crucial roles in spermatogenesis and sperm motility acquirement. (C) 2014 Elsevier Inc. All rights reserved.
  • Species and inter-individual differences in metabolic capacity of di(2-ethylhexyl)phthalate (DEHP) between human and mouse livers, Yuki Ito, Michihiro Kamijima, Chie Hasegawa, Masahiro Tagawa, Toshio Kawai, Mio Miyake, Yumi Hayashi, Hisao Naito, Tamie Nakajima, ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE, 19, (2) 117 - 125,   2014年03月, This study was conducted to assess inter-species and inter-individual differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and mice. The activities of four DEHP-metabolizing enzymes [lipase, UDP-glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various ages and in eight 129/Sv male mice. Microsomal lipase activity was significantly lower in humans than in mice. The V (max)/K (m) value in humans was one-seventh of that in mice, microsomal UGT activity in humans was a sixth of that in mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in humans than in mice. The total amount of DEHP urinary metabolites and the concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact mice than in the U.S. general population based on data reported elsewhere, regardless of the similar estimated DEHP intake between these mice and the human reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the latter than in the former. Of note, inter-subject variability in the activities of all enzymes measured was 10-26-fold. The inter-individual variation in the metabolism of DEHP in humans may be greater than the difference between mice and humans (inter-species variation), and both may affects the risk assessment of DEHP.
  • Organophosphate agents induce plasma hypertriglyceridemia in mouse via single or dual inhibition of the endocannabinoid hydrolyzing enzyme(s), Himiko Suzuki, Yuki Ito, Yuki Noro, Mamoru Koketsu, Michihiro Kamijima, Motohiro Tomizawa, TOXICOLOGY LETTERS, 225, (1) 153 - 157,   2014年02月, Diverse serine hydrolases including endocannabinoid metabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have been suggested as secondary targets for organophosphate (OP) agents to exert adverse toxic effects such as lipid homeostasis disruption. The goal of this investigation is to verify that a major OP insecticide fenitrothion (FNT) induces plasma hypertriglyceridemia through the inhibition of FAAH and/or MAGL in comparison with that elicited by isopropyl dodecylfluorophosphonate (IDFP), a potent FAAH/MAGL inhibitor. Fasted mice were treated intraperitoneally with FNT or IDFP and were subsequently sacrificed for evaluations of plasma triglyceride (TG) levels and liver FAAH/MAGL activities. Plasma TG levels were significantly enhanced by the FNT or IDFP treatment (1.7- or 4.8-fold, respectively) compared with that of vehicle control. The IDFP exposure reduced the liver FAAH and MAGL activities, whereas the FNT exposure led to the preferential FAAH inhibition. The brain acetylcholinesterase was almost unaffected by the FNT or IDFP treatment, thus leading to no neurotoxic sign. Intriguingly, the TG elevations were averted by concomitant administration with the cannabinoid receptor antagonist AM251. The present findings suggest that OP agents induce plasma hypertriglyceridemia in mouse through single or dual inhibition of FAAH or/and MAGL, apparently leading to overstimulation of cannabinoid signal regulating energy metabolism. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
  • 子どもの健康と環境に関する全国調査(エコチル調査)―概要並びに東海地区における実施状況と今後の展望―, 上島通浩, 榎原毅, 宮田麻衣子, 加藤沙耶香, 若林千鶴子, 伊藤由起, 齋藤伸治, 杉浦真弓, 東海産婦人科学会雑誌, 51, 9 - 15,   2014年, 招待有り
  • 胎生期フタル酸ジ-2-エチルヘキシル曝露による次世代影響-可塑剤が引き起こす次世代影響の原因-, 林由美, 伊藤由起, 那須民江, 日本衛生学雑誌, 69, (2) 86 - 91,   2014年, 査読有り, 招待有り
  • Chapter 3. Hypersensitivity Dermatitis and Hepatitis. Trichloroethylene: Toxicity and Health Risks, Kamijima M, Wang H, Yamanoshita O, Ito Y, Nakajima T, Gilbert KM and Blossom SJ ed. Trichloroethylene: Toxicity and Health Risks., 37 - 52,   2014年, 招待有り
  • Occupational trichloroethylene hypersensitivity syndrome: Human herpesvirus 6 reactivation and rash phenotypes, Michihiro Kamijima, Hailan Wang, Osamu Yamanoshita, Yuki Ito, Lihua Xia, Yukie Yanagiba, Cishan Chen, Ai Okamura, Zhenlie Huang, Xinxiang Qiu, Xiangrong Song, Tingfeng Cai, Lili Liu, Yichen Ge, Yingyu Deng, Hisao Naito, Tetsushi Yoshikawa, Mikiko Tohyama, Laiyu Li, Hanlin Huang, Tamie Nakajima, JOURNAL OF DERMATOLOGICAL SCIENCE, 72, (3) 218 - 224,   2013年12月, Background: Trichloroethylene (TCE) is an industrial solvent which can cause severe generalized dermatitis, i.e., occupational ICE hypersensitivity syndrome. Reactivation of latent human herpesvirus 6 (HHV6) can occur in such patients, which has made TCE known as a causative chemical of drug-induced hypersensitivity syndrome (DIHS). Objective: This study aimed to clarify HHV6 status, cytokine profiles and their association with rash phenotypes in patients with TCE hypersensitivity syndrome. Methods: HHV6 DNA copy numbers, anti-HHV6 antibody titers, and cytokines were measured in blood prospectively sampled 5-7 times from 28 hospitalized patients with the disease. Results: The patients (19 had exfoliative dermatitis (ED) and 9 had non-ED type rash) generally met the diagnostic criteria for DIHS. Viral reactivation defined as increases in either HHV6 DNA (>= 100 genomic copies/10(6) peripheral blood mononuclear cells) or antibody titers was identified in 24 (89%) patients. HHV6 DNA, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-5, IL-6 and IL-10 concentrations were remarkably higher in the patients than in the healthy workers (p < 0.01). Positive correlations between HHV6 DNA, TNF-alpha, IFN-gamma, IL-6 and IL-10 were significant (p < 0.05) except for that between HHV6 DNA and IFN-gamma. An increase in HHV6 DNA was positively associated with an increase in TNF-alpha on admission (p < 0.01). HHV6 DNA, the antibody titers, TNF-alpha and IL-10 concentrations were significantly higher in ED than in the non-ED type (p < 0.05). Conclusion: Reactivated HHV6 and the increased cytokines could be biomarkers of TCE hypersensitivity syndrome. The higher-level reactivation and stronger humoral responses were associated with ED-type rash. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Sex Differences in Metabolism of Trichloroethylene and Trichloroethanol in Guinea Pigs, Yui Hibino, Hailan Wang, Hisao Naito, Na Zhao, Dong Wang, Xiaofang Jia, Hongling Li, Xiangrong Song, Lili Liu, Yongshun Huang, Yuki Ito, Hanlin Huang, Michihiro Kamijima, Tamie Nakajima, JOURNAL OF OCCUPATIONAL HEALTH, 55, (6) 443 - 449,   2013年11月, 査読有り, Objectives: Trichloroethylene (TRI) has the potential to cause generalized dermatitis complicated with hepatitis. The guinea pig maximization test (GPMT) also suggests that both TRI and its metabolite trichloroethanol (ICE) exhibit immunogenicity and possible sex differences in guinea pigs. However, TRI and TOE metabolisms in guinea pigs have not been elucidated in detail. The first issue to clarify may be the sex differences in relation to the immunogenicity, Methods: We collected urine from Hartley male and female guinea pigs 24 hours after intracutaneous injection of TRI, TCE or trichloroacetic acid (TCA) during a GPMT and measured the urinary metabolites by gas chromatography-mass spectrometry. Results: After TRI treatment, the amount of TCA was significantly greater in females than males, while there was no sex difference in the total amount (TCA + TOE). TCA was only detected in urine after TCA treatment. Interestingly, not only TCE but also TCA was detected in urine of both sexes after TOE treatment, and the amount of TCA was also greater in females than males. An additional experiment showed that TOE treatment did not result in the detection of urinary TCA in cytochrome P450 (CYP)2E1-null mice but did in wild-type mice, suggesting the involvement of CYP2E1 in the metabolism from TOE to TCA. The constitutive expression of CYP2E1 in the liver of guinea pigs was greater in females than males. Conclusions: The sex difference in urinary TCA excretion after TRI and TOE treatments may be due to variation of the constitutive expression of CYP2E1.
  • Anticholinesterase insecticide action at the murine male reproductive system, Yuki Noro, Motohiro Tomizawa, Yuki Ito, Himiko Suzuki, Keisuke Abe, Michihiro Kamijima, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 23, (19) 5434 - 5436,   2013年10月, The present report describes for the first time that anticholinesterase type insecticides specifically inhibit the fatty acid amide hydrolase and/or monoacylglycerol lipase, as secondary target(s), in the murine male reproductive system (testis and epididymis cauda), thereby presumably being involved with spermatotoxicity such as deformity, underdevelopment, and reduced motility. (C) 2013 Elsevier Ltd. All rights reserved.
  • A Potential Target for Organophosphate Insecticides Leading to Spermatotoxicity, Himiko Suzuki, Motohiro Tomizawa, Yuki Ito, Keisuke Abe, Yuki Noro, Michihiro Kamijima, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 61, (41) 9961 - 9965,   2013年10月, Organophosphate (OP) insecticides as an anticholinesterase also act on the diverse serine hydrolase targets, thereby revealing secondary or unexpected toxic effects including male reproductive toxicity. The present investigation detects a possible target molecule(s) for OP-induced spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) from a chemical standpoint. The activity-based protein profiling (ABPP) approach with a phosphonofluoridate fluorescent probe pinpointed the molecular target for fenitrothion (FNT, a major OP insecticide) oxon (bioactive metabolite of FNT) in the mouse testicular membrane proteome, i.e., FNT oxon phosphorylates the fatty acid amide hydrolase (FAAH), which plays pivotal roles in spermatogenesis and sperm motility acquirement. Subsequently, mice were treated orally with vehicle or FNT for 10 days, and FAAH activity in testis or epididymis cauda was markedly reduced by the subacute exposure. ABPP analysis revealed that FAAH was selectively inhibited among the FNT-treated testicular membrane proteome. Accordingly, FAAH is a potential target for OP-elicited spermatotoxicity.
  • Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice, Ryosuke Nakashima, Yumi Hayashi, Khalequzzaman Md, Xiaofang Jia, Dong Wang, Hisao Naito, Yuki Ito, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGY, 309, 52 - 60,   2013年07月, Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPAR alpha), peroxisome proliferator-activated receptor alpha-null (Ppar alpha-null) and humanized PPAR alpha (hPPAR alpha) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, alpha-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPAR alpha mice than in Ppara-null and hPPAR alpha mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPAR alpha mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, alpha-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPAR alpha mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPAR alpha mice, similarly to triglyceride levels. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
  • Anticholinesterase insecticide action at the endocannabinoid system eliciting spermatotoxicity., Noro Y, Tomizawa M, Ito Y, Suzuki H, Abe K, Kamijima M, Bioorg Med Chem Lett, 23, 5434 - 5436,   2013年
  • Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice, Dong Wang, Michihiro Kamijima, Ai Okamura, Yuki Ito, Yukie Yanagiba, Xiao-fang Jia, Hisao Naito, Jun Ueyama, Tamie Nakajima, REPRODUCTIVE TOXICOLOGY, 34, (4) 489 - 497,   2012年12月, The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 mu mol/kg/day) or cis-permethrin (90 mu mol/kg/clay) alone or in combination (100 mu mol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon-permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident. (C) 2012 Elsevier Inc. All rights reserved.
  • Effect of nanoparticle-rich diesel exhaust on testicular and hippocampus steroidogenesis in male rats, Nozomi Yamagishi, Yuki Ito, Doni Hikmat Ramdhan, Yukie Yanagiba, Yumi Hayashi, Dong Wang, Chun Mei Li, Shinji Taneda, Akira K. Suzuki, Kazuyoshi Taya, Gen Watanabe, Michihiro Kamijima, Tamie Nakajima, INHALATION TOXICOLOGY, 24, (8) 459 - 467,   2012年07月, 査読有り, Background: Nanoparticle-rich diesel exhaust (NR-DE) has potentially adverse effects on testicular steroidogenesis. However, it is unclear whether NR-DE influences steroidogenic systems in the brain. Objective: To investigate the effect of NR-DE on hippocampal steroidogenesis of adult male rats in comparison with its effect on the testis. Methods: F344 male rats (8-week-old) were randomly divided into four groups (n = 8 or 9 per group) and exposed to clean air with 4.6 +/- 3.2 mu g/m(3) in mass concentration, NR-DE with 38 +/- 3 mu g/m(3) (a level nearly equivalent to the environmental standard in Japan (low NR-DE)), NR-DE with 149 +/- 8 mu g/m(3) (high NR-DE), or filtered diesel exhaust with 3.1 +/- 1.9 mu g/m(3) (F-DE), for 5 hours/day, 5 days/week, for 1, 2 or 3 months. F-DE was prepared by removing only particulate matters from high NR-DE with an HEPA filter. Results: Exposures to the high NR-DE for 1 month, and low NR-DE for 2 months, significantly increased or tended to increase plasma and testicular testosterone levels compared to clean air exposure, which might have resulted from the increased expression of mRNA of steroidogenic acute regulatory protein and its protein in the testes of rats. In the hippocampus, high NR-DE exposure for 1 month significantly increased the androstendione level compared to the clean air exposure, while no significant difference was observed in the steroidogenesis between fresh air exposure and any exposure to NR-DE or F-DE. Conclusion: NR-DE may influence steroidogenic enzymes in the testis, but not those in the hippocampus.
  • The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model, Xiaofang Jia, Hisao Naito, Husna Yetti, Hazuki Tamada, Kazuya Kitamori, Yumi Hayashi, Nozomi Yamagishi, Dong Wang, Yukie Yanagiba, Yuki Ito, Juncai Wang, Naoki Tanaka, Katsumi Ikeda, Yukio Yamori, Tamie Nakajima, LIFE SCIENCES, 90, (23-24) 934 - 943,   2012年06月, Aims: Eicosapentaenoic acid (EPA) can ameliorate certain liver lesions involved in non-alcoholic steatohepatitis (NASH). A previous study has found that stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats fed a high fat-cholesterol (HFC) diet developed fibrotic steatohepatitis with histological similarities to NASH. This study evaluated the potential effects and mechanisms of action of EPA supplementation using this rodent model. Main Methods: Male rats were randomly assigned to groups that were fed with either the stroke-prone (SP) diet or HFC diet with or without EPA for 2,8 and 14 weeks, respectively. The liver histopathology, biochemical features, mRNA and protein levels, and nuclear factor-kappa B (NF-kappa B) DNA binding activity were determined. Key findings: The SP diet-fed rats presented normal livers. Conversely, the HFC diet-fed rats developed microvesicular/macrovesicular steatosis, inflammation, ballooning degeneration and severe fibrosis. At 2 weeks, the administration of EPA inhibited hepatic inflammatory recruitment by blocking the phosphorylation of inhibitor of KB-alpha (I kappa B alpha), which antagonizes the NF-kappa B activation pathway. The dietary supplementation of EPA for 8 weeks ameliorated hepatic triglyceride accumulation and macrovesicular steatosis by inhibiting the HFC diet-induced decrease in the protein levels of enzymes involved in fatty acid beta-oxidation including carnitine palmitoyltransferase 1, very long chain acyl-CoA dehydrogenase and peroxisomal bifunctional protein. Although the administration of EPA elicited no histologically detectable effects on severe fibrosis at 14 weeks, it restored an HFC diet-induced decline in hepatic adenosine triphosphate (ATP) levels and suppressed ballooning degeneration, suggesting that EPA may inhibit HFC diet-induced ATP loss and cell death. Significance: Initial amelioration of the inflammation and steatosis in the rats after EPA supplementation indicates a possibility to treat steatohepatitis. Additionally, this study provides new insights into the roles of EPA in hepatic ATP depletion and subsequent hepatocellular injury during severe fibrosis. (c) 2012 Elsevier Inc. All rights reserved.
  • Urinary concentrations of organophosphorus insecticide metabolites in Japanese workers, Jun Ueyama, Isao Saito, Takaaki Kondo, Tomoko Taki, Akiko Kimata, Shun Saito, Yuki Ito, Katsuyuki Murata, Toyoto Iwata, Masahiro Gotoh, Eiji Shibata, Shinya Wakusawa, Michihiro Kamijima, CHEMOSPHERE, 87, (11) 1403 - 1409,   2012年06月, A recent development in analytical chemistry has enabled us to monitor systemic organophosphorus insecticide (OP) exposure at individual levels. At present, however, limited data are currently available on urinary OP metabolite levels worldwide. The purpose of this study was to assess urinary dialkylphosphate (DAP) concentrations in Japanese workers. Urine samples were collected in both summer and winter from 339 Japanese adults who worked as food distributors (FDs, n = 164), apple farmers (AFs, n = 147) and pest control operators (PCOs, n = 28). DAPs were measured by gas chromatography-mass spectrometry after derivatization with pentafluorobenzylbromide. Dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP) and diethylthiophosphate (DETP) were detected in the urine of over 87% of the studied populations in both seasons. The geometric mean values of total DAPs (nmol g(-1) creatinine), DMP, DMTP, DEP and DETP (mu g g(-1) creatinine) in summer and winter were 106.7 and 98.3, 7.0 and 3.8, 3.4 and 4.5, 0.8 and 1.5, and 0.3 and 0.2 for the FDs, 440.8 and 197.7, 33.1 and 10.8, 10.1 and 5.8, 4.2 and 4.7 and 1.6 and 0.8 for the AFs, and 473.4 and 284.6, 28.9 and 22.2, 17.6 and 4.6, 3.5 and 4.4, and 0.5 and 0.6 for the PCOs, respectively, thereby revealing significantly higher concentrations in AFs and PCOs groups than in the FDs in both seasons except for winter DMTP. These DAP concentrations were approximately the same or at lower levels compared with those reported in the previous literature. This is one of the first studies to demonstrate urinary DAP concentrations in Japanese adults. (C) 2012 Elsevier Ltd. All rights reserved.
  • New analytical method for sensitive quantification of urinary 3-methyl-4-nitrophenol to assess fenitrothion exposure in general population and occupational sprayers, Ai Okamura, Isao Saito, Jun Ueyama, Yuki Ito, Tamie Nakajima, Michihiro Kamijima, TOXICOLOGY LETTERS, 210, (2) 220 - 224,   2012年04月, The measurement of blood cholinesterase (ChE) activities is adopted worldwide for biological monitoring of exposure to organophosphorus insecticides (OPs). Recent development of analytical chemistry has made sensitive quantification possible of non-specific OP metabolites, dialkylphosphates, in urine as a biomarker of low-level OP exposure. In this study, we established a method for quantification of urinary 3-methyl-4-nitrophenol (MNP), a specific metabolite of fenitrothion (FNT), and a parathion metabolite p-nitrophenol (PNP), using gas chromatography-mass spectrometry. The limits of detection of MNP and PNP were 0.3 and 0.5 mu g/L, respectively. The method enabled the quantification of both free and conjugated metabolites. This method was actually applied to monitor human urine in summer and winter in FNT sprayers (N = 29 and 9, respectively) and control workers (N = 17 and 29, respectively). Geometric mean total MNP concentrations (mu g/g creatinine) in the FNT sprayers (28.8 in summer and 8.6 in winter) were significantly higher than those of the controls (3.1 in summer and 2.3 in winter) in both seasons. Among the sprayers, total MNP concentrations in summer were significantly higher than in winter. In contrast, no significant difference in total PNP concentrations was observed between FNT sprayers (geometric mean 3.4 in summer and 3.0 in winter) and controls (3.6 in summer and 2.1 in winter). No seasonal difference was observed in each group. In conclusion, the present new method is sensitive enough for biological monitoring of FNT and parathion metabolites even in a non-spraying population. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Differences in metabolite burden of di(2-ethylhexyl)phthalate in pregnant and postpartum dams and their offspring in relation to drug-metabolizing enzymes in mice, Yumi Hayashi, Yuki Ito, Yukie Yanagiba, Michihiro Kamijima, Hisao Naito, Tamie Nakajima, ARCHIVES OF TOXICOLOGY, 86, (4) 563 - 569,   2012年04月, Di(2-ethylhexyl)phthalate (DEHP) induced adverse effects on mice offspring, and the metabolite mono(2-ethylhexyl)phthalate (MEHP) may be essential to determine the toxicity. In this experiment, we measured liver MEHP levels and the factors determining the metabolism, two enzyme activities [lipase and uridine 5'-diphosphate-glucuronosyltransferase (UGT)] or expression of cytochrome P450 4A14 (CYP4A14) in dams (on gestational day 18 and postnatal day 2) and their offspring. MEHP concentrations in the liver from pregnant dams were 1.5 times higher than those of postpartum dams at exposure to 0.05% DEHP. Accordingly, MEHP concentrations were 1.7 times higher in fetuses than in pups at the dose. Interestingly, lipase activity was 1.8-fold higher in pregnant dams than postpartum ones, but no such difference was noted in the activity between fetuses and pups. UGT activity was also 1.5-fold higher in pregnant dams than postpartum ones, whereas the activity in the fetuses was 1/2 that of pups. No difference was noted in CYP4A14 levels between pregnant and postpartum mice, whereas the levels in the fetuses were < 1/10 those of pups. DEHP exposure did not influence lipase activity, whereas it slightly enhanced UGT activity and exclusively increased CYP4A14 levels in pregnant and/or postpartum dams. Taken together, the higher MEHP levels in pregnant dams than postpartum ones may be primarily due to higher lipase activities in pregnant dams, which may closely reflect those in fetuses and pups.
  • Modulation of ammonium perfluorooctanoate-induced hepatic damage by genetically different PPARα in mice., Nakagawa Tomohiko, Ramdhan Doni Hikmat, Tanaka Naoki, Naito Hisao, Tamada Hazuki, Ito Yuki, Li Yufei, Hayashi Yumi, Yamagishi Nozomi, Yanagiba Yukie, Aoyama Toshifumi, Gonzalez Frank J, Nakajima Tamie, Archives of toxicology, 86, (1) 63 - 74,   2012年01月
  • Simultaneous changes in high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis and those underlying molecular mechanisms in novel SHRSP5/Dmcr rat., Moriya Takashi, Kitamori Kazuya, Naito Hisao, Yanagiba Yukie, Ito Yuki, Yamagishi Nozomi, Tamada Hazuki, Jia Xiaofang, Tsuchikura Satoru, Ikeda Katsumi, Yamori Yukio, Nakajima Tamie, Environmental health and preventive medicine, 17, (6) 444 - 56,   2012年
  • Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver., Ito Yuki, Nakamura Toshiki, Yanagiba Yukie, Ramdhan Doni Hikmat, Yamagishi Nozomi, Naito Hisao, Kamijima Michihiro, Gonzalez Frank J, Nakajima Tamie, PPAR research, 2012,   2012年
  • Hepatic peroxisome proliferator-activated receptor α may have an important role in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice., Hayashi Y, Ito Y, Yamagishi N, Yanagiba Y, Tamada H, Wang D, Ramdhan DH, Naito H, Harada Y, Kamijima M, Gonzales FJ, Nakajima T, Toxicology, 289, (1) 1 - 10,   2011年10月
  • Ammonium perfluorooctanoate may cause testosterone reduction by adversely affecting testis in relation to PPARα., Li Y, Ramdhan DH, Naito H, Yamagishi N, Ito Y, Hayashi Y, Yanagiba Y, Okamura A, Tamada H, Gonzalez FJ, Nakajima T, Toxicol Lett, 205, (3) 265 - 272,   2011年09月
  • ~ナノ粒子を多く含むディーゼル排気ガス曝露による肝臓への影響~ 第81回日本衛生学会若手プロジェクト研究助成ミニシンポジウム「ディーゼル排気ガス中のナノ粒子による健康影響―動物実験の知見から―」ミニ特集, 山岸希, 伊藤由起, ラムダンドニヒクマット, 那須民江, 日本衛生学雑誌, 66, (4) 634 - 7,   2011年
  • ~ナノ粒子を多く含むディーゼル排気ガス曝露による肝臓への影響~ 第81回日本衛生学会若手プロジェクト研究助成ミニシンポジウム「ディーゼル排気ガス中のナノ粒子による健康影響―動物実験の知見から―」ミニ特集, 伊藤由起, ラムダンドニヒクマット, 柳場由絵, 山岸希, 上島通浩, 那須民江, 日本衛生学雑誌, 66, (4) 638 - 42,   2011年, 査読有り, 招待有り
  • 胎生期フタル酸ジ-2-エチルヘキシル曝露による低栄養環境と生活習慣病. 第81回日本衛生学会次世代影響連携研究会ミニ特集, 林由美, 伊藤由起, 那須民江, 日本衛生学雑誌, 67, (1) 22 - 5,   2011年, 査読有り, 招待有り
  • Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol, Daichi Nakamura, Yukie Yanagiba, Zhiwen Duan, Yuki Ito, Ai Okamura, Nobuyuki Asaeda, Yoshiaki Tagawa, ChunMei Li, Kazuyoshi Taya, Shu-Yun Zhang, Hisao Naito, Doni Hikmat Ramdhan, Michihiro Kamijima, Tamie Nakajima, TOXICOLOGY LETTERS, 194, (1-2) 16 - 25,   2010年04月, Bisphenol A (BPA) causes reproductive toxicities, but the mechanisms are still unclear. In the present study, we sought to clarify these mechanisms in comparison with those of 17 beta-estradiol (E2). Prepubertal Wistar/ST male rats (4 weeks old) were subcutaneously administered BPA (0, 20, 100 and 200 mg/kg/day) or E2 (10 and 100 mu g/kg/clay) for 6 weeks. Both BPA and E2 treatments decreased plasma and testicular testosterone levels, and plasma luteinizing hormone (LH), but not E2 and follicle-stimulating hormone levels, though E2 treatment increased its plasma level. In relation to the decreased testosterone levels, BPA and E2 decreased expressions of steroidogenic enzymes and cholesterol carrier protein in Leydig cells. Thus, decreased testosterone levels in plasma might have resulted from decreased expressions of these enzymes and protein as well as from decreased plasma LH levels. Interestingly, the changes in steroidogenic enzymes and carrier protein were observed at lower levels of exposure to BPA or E2 than those inhibiting plasma LH levels. Microscopically, 200 mg/kg BPA and 100 mu g/kg E2 significantly decreased Leydig cell numbers in the testis. In addition, BPA and E2 also decreased expression of estrogen receptor a-mRNA, which might be related to the decreased numbers of Leydig cells. Thus, BPA directly affects not only the Leydig cells but also the pituitary gland, but the former may be impaired at lower exposure concentrations than the latter. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
  • DEHP-induced reproductive and developmental toxicity and PPARα. Bisphenol A and Phthalates: Use, Health Effects and Environmental Risks., Ito Y, Hayashi Y, Nakajima T, BisphenolA and Phthalates: Use, Health Effects and Environmental Risks. Bradley C. Vaughn ed. Nova Science Publishers, Inc., 175-185,   2010年
  • Differential Response to Trichloroethylene-Induced Hepatosteatosis in Wild-Type and PPARα-Humanized Mice., Ramdhan DH, Kamijima M, Wang D, Ito Y, Naito H, Yanagiba Y, Hayashi Y, Tanaka N, Aoyama T, Gonzalez FJ, Nakajima T, Environ Health Perspect, 118(11): 1557-63,   2010年
  • シックハウス症候群・化学物質過敏症への対応, 上島通浩, 酒井潔, 伊藤由起, 榎原毅, 柴田英治, 現代医学, 58, (1) 29 - 37,   2010年
  • Nanoparticle-rich diesel exhaust may disrupt testosterone biosynthesis and metabolism via growth hormone, Doni Hikmat Ramdhan, Yuki Ito, Yukie Yanagiba, Nozomi Yamagishi, Yumi Hayashi, ChunMei Li, Shinji Taneda, Akira K. Suzuki, Gen Watanabe, Kazuyoshi Taya, Michihiro Kamijima, Tamie Nakajima, TOXICOLOGY LETTERS, 191, (2-3) 103 - 108,   2009年12月, We previously reported that exposure to low (22.5 +/- 02 nm in diameter, 154 +/- 10 mu g/m(3) in mass weight, 227 x 10(5)/cm(3) in mean number concentration). and medium (26.1 +/- 05 nm, 364 +/- 12 mu g/m(3). 511 x 10(5)/cm(3)) concentrations of nanoparticle-rich diesel exhaust (NR-DE) for 1 and 2 months (5 h/day, 5 days/week) significantly increased plasma testosterone in male Fischer 344 rats, whereas exposure to a high concentration (27.1 +/- 05 nm, 168.8 +/- 2.7 mu g/m(3), 1.36 x 10(6)/cm(3)) did riot The present study attempts to clarify the mechanism of this elevation. Low and medium exposures to NR-DE for 1 and 2 months significantly increased steroidogenic acute regulatory protein (StAR)- and cytochrome P450 side-chain cleavage (P450scc)-mRNA and their protein expressions in the testis of rats. in which the elevation pattern was very similar to that of plasma testosterone levels. Interestingly, both exposure levels for 1 month significantly increased growth hormone (GH) receptor expression in the testis, and low exposure also increased testicular insulin-like growth factor I-mRNA levels and hepatic microsomal cytochrome P450 2C11-mRNA and their protein levels in rats These two factors are thought to be related to growth hormone secretion. Disruption of testosterone biosynthesis by NR-DE exposure may be a mode of action for reproductive toxicity. which may. in part, be regulated by increasing StAR and P450scc expressions via GH signalling. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Comparison of urinary concentrations of 3-phenoxybenzoic acid among general residents in rural and suburban areas and employees of pest control firms, Akiko Kimata, Takaaki Kondo, Jun Ueyama, Kanami Yamamoto, Junko Yoshitake, Kenji Takagi, Koji Suzuki, Takashi Inoue, Yoshinori Ito, Nobuyuki Hamajima, Michiro Kamijima, Masahiro Gotoh, Eiji Shibata, INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 82, (10) 1173 - 1178,   2009年11月, 査読有り, Objectives The purpose of this study is to determine the levels of urinary 3-phenoxybenzoic acid (3-PBA) among general populations in rural and suburban areas and employees of pest control firms to evaluate the differences in the level of environmental or occupational pyrethroid (PYR) pesticides to which those populations are exposed. Methods Spot urine specimens were collected from male residents in a rural area (n = 143) and male residents in a suburban area (n = 66) in August of 2005 and 2007, respectively. Male employees of pest control firms, who also provided their urine specimens at the time of a health-checkup in August 2007, were classified either as sprayers (n = 14) or as non-sprayers ( n = 16) according to the presence of spraying during the pre-checkup week. Urinary concentrations of 3-PBA were determined using gas chromatography-mass spectrometry and corrected for the urinary creatinine concentrations. An analysis of covariance was used to examine the statistical difference in 3-PBA concentrations between these four groups after adjustment for age, body mass index, and current smoking/drinking habits. Results Multiple comparisons indicated no differences in adjusted 3-PBA concentrations between the groups of general residents from the rural areas (0.33 mu g/g cre in geometric mean) and suburban area (0.51 mu g/g cre). The group of sprayers showed a much higher level of 3-PBA concentrations (25.0 mu g/g cre) than the other three groups. A statistically significant difference, though to a lesser extent, was also exhibited in 3-PBA concentrations between the group of non-sprayers (5.6 mu g/g cre) and that of general residents. Conclusions The results indicated that the levels of background low-dose exposure to PYRs are not likely to differ evidently among general populations according to the area of residence. Moreover, employees of pest control firms, who have been away from PYR spraying operations for a week or more, still retain much higher urinary 3-PBA concentrations than general populations.
  • Microgram-order ammonium perfluorooctanoate may activate mouse peroxisome proliferator-activated receptor alpha, but not human PPAR alpha, Toshiki Nakamura, Yuki Ito, Yukie Yanagiba, Doni Hikmat Ramdhan, Yasuhide Kono, Hisao Naito, Yumi Hayashi, Yufei Li, Toshifumi Aoyama, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGY, 265, (1-2) 27 - 33,   2009年11月, Perfluorooctanoic acid (PFOA) is a ligand for peroxisome proliferator-activated receptor (PPAR)alpha, which exhibits marked species differences in expression and function, especially between rodents and humans. We investigated the functional difference in PFOA response between mice and humans, using a humanized PPAR alpha transgenic mouse line. Three genotyped mice, 129/5v wild-type (mPPAR alpha), Ppar alpha-null mice and humanized PPAR alpha (hPPAR alpha) mice (8-week-old males) were divided into three groups: the first was treated with water daily for 2 weeks by gavage (control group), and the remaining two groups were treated with 0.1 and 0.3 mg/kg ammonium perflurooctanate (APFO), respectively, for 2 weeks by gavage. The APFO dosages used did not influence the plasma triglyceride or total cholesterol levels in any mouse line, but the high dose increased both hepatic lipid levels only in mPPAR alpha mice. APFO increased mRNA and/or protein levels of PPAR alpha target genes cytochrome P450 Cyp4a10, peroxisomal thiolase and bifunctional protein only in the liver of mPPAR alpha mice, but not in Ppar alpha-null or hPPAR alpha mice. This chemical also increased expression of mitochondrial very long chain acyl-CoA dehydrogenase only in the liver of mPPAR alpha mice. Taken together, human PPAR alpha may be less responsive to PFOA than that of mice when a relatively low dose is applied. This information may be very valuable in considering whether PFOA influences the lipid metabolism in humans. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Octachlorostyrene Induces Cytochrome P450, UDP-glucuronosyltransferase, and Sulfotransferase via the Aryl Hydrocarbon Receptor and Constitutive Androstane Receptor, Yukie Yanagiba, Yuki Ito, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGICAL SCIENCES, 111, (1) 19 - 26,   2009年09月, Octachlorostyrene (OCS) is a byproduct produced in the process of synthesis of chlorinated compounds. There are some reports concerning environmental contamination by OCS, but few on the toxicological effects on human. Drug-metabolizing enzymes may play an important role in toxicity through metabolic activation or deactivation of OCS. In this study, we investigated whether OCS influences these enzymes using wild-type and aryl hydrocarbon receptor (Ahr)-null mice; AhR regulates cytochrome P450 (CYP) 1A, UDP-glucuronosyltransferase (UGT), or sulfotransferase (SULT). Both mouse lines were treated with OCS (0, 32, and 64 mu mol/kg) for 4 days by gavage. As a reference, the mice were treated with 20 mg/kg 3-methylcholanthrene (3MC) for 4 days. OCS treatment increased the expression of CYP 1A1 and CYP1A2 mRNA and ethoxyresorfin O-deethylase activity only in the wild-type mice, similar to that of the AhR activator 3MC. OCS treatment increased expression of UGT1A6 and SULT 1A1 mRNA and their associated enzyme activities only in Ahr-null mice, whereas 3MC still influenced these enzymes only in wild-type mice. OCS induced constitutive androstane receptor (CAR) only in Ahr-null mice, and the target gene CYP2B10 mRNA was induced more strongly in Ahr-null mice than in wild-type mice. 3MC slightly induced CYP2B10 mRNA only in the wild-type mice. These results suggest that CAR is involved in regulation of the UGT and SULT genes by OCS. Thus, OCS may regulate CYP1A via AhR, whereas it controls UGT1A6 and SULT1A via CAR.
  • Effects of inhaled nanoparticle-rich diesel exhaust on regulation of testicular function in adult male rats, ChunMei Li, Shinji Taneda, Kazuyoshi Taya, Gen Watanabe, Xuezheng Li, Yuji Fujitani, Yuki Ito, Tamie Nakajima, Akira K. Suzuki, INHALATION TOXICOLOGY, 21, (8-11) 803 - 811,   2009年07月, We investigated the effects of nanoparticle-rich diesel exhaust (NR-DE) on reproductive function. Eight-week-old male F344 rats were divided into 12 experimental groups and exposed to either whole NR-DE at low (15.37 mu g/m(3), 2.27 x 10(5) particles/cm(3)), middle (36.35 mu g/m(3), 5.11 x 10(5) particles/cm(3)), or high (168.84 mu g/m(3), 1.36 x 10(6) particles/cm3) concentrations or clean air for 4, 8, or 12 weeks (5 hours/day, 5 days/week). NR-DE exposure for 4 or 8 weeks did not affect body weight; however, body weight was significantly decreased in rats exposed to low- or high-concentration NR-DE for 12 weeks compared to the control group. Relative weights of testes, epididymides, seminal vesicles, and prostate had increased non-significantly in all NR-DE-exposed rats at 4, 8, and 12 weeks. Adrenal gland relative weights were significantly increased at 4 weeks in rats exposed to low-concentration NR-DE. Plasma luteinizing hormone and follicle stimulating hormone concentrations did not change significantly. Plasma testosterone concentrations were significantly increased after exposure to low- or middle-concentration NR-DE for 4 or 8 weeks compared to controls. Plasma immunoreactive (ir-) inhibin concentrations were significantly increased after exposure to high-concentration NR-DE for 4 weeks or middle- or high-concentration NR-DE for 12 weeks compared to controls. Testicular testosterone concentrations were significantly increased at 4, 8, and 12 weeks after exposure to low-concentration NR-DE compared to controls. In contrast, with exposure to low- or high-concentration NR-DE, testicular ir-inhibin concentrations were significantly greater than in controls, but only at 4 weeks. These results suggest that NR-DE inhalation disrupts the endocrine activity of the male reproductive system.
  • Urinary excretion of 3-phenoxybenzoic acid in middle-aged and elderly general population of Japan, Jun Ueyama, Akiko Kimata, Michihiro Kamijima, Nobuyuki Hamajima, Yoshinori Ito, Koji Suzuki, Takashi Inoue, Kanami Yamamoto, Kenji Takagi, Isao Saito, Ken-ichi Miyamoto, Takaaki Hasegawa, Takaaki Kondo, ENVIRONMENTAL RESEARCH, 109, (2) 175 - 180,   2009年02月, 査読有り, Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan, despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5 +/- 9.8 years of age. mean +/- S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 mu g/l. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n = 87) and the remaining general group without occupational exposure (n = 448) were 0.38 and 0.29 mu g/l, respectively, ranging from <LOD to 17.09 mu g/l. No significant differences in urinary 3-PBA concentrations were shown between these two groups. Moreover, 3-PBA concentrations were found comparable to those reported in some countries. The present study is, to our knowledge, the first report of a biological monitoring study of urinary 3-PBA, which elucidated the background environmental exposure level of PYR in the Japanese general population without occupational exposure. Further nationwide studies covering different seasons and age distribution are needed to monitor the urinary 3-PBA levels in Japan. (C) 2008 Elsevier Inc. All rights reserved.
  • Relationship between dietary habits and urinary concentrations of 3-phenoxybonzoic acid in a middle-aged and elderly general population in Japan, Kimata A, Kondo T, Ueyama J, Yamamoto K, Kamijima M, Suzuki K, Inoue T, Ito Y, Hamajima N, Environmental Health and Preventive Medicine, 14, (3) 173 - 179,   2009年, 査読有り
  • "Hypothesis of Seven Balances": Molecular mechanisms behind alcoholic liver diseases and association with PPARα, Moriya T, Naito H, Ito Y, Nakajima T, J Occup Health, 51(5): 391-403,   2009年
  • Broken Sperm, Cytoplasmic Droplets and Reduced Sperm Motility Are Principal Markers of Decreased Sperm Quality Due to Organophosphorus Pesticides in Rats., Okamura A, Kamijima M, Ohtani K, Yamanoshita O, Nakamura D, Ito Y, Miyata M, Ueyama J, Suzuki T, Imai R, Takagi K, Nakajima T, J Occup Health, 51(6): 478-487,   2009年
  • Molecular mechanism of trichloroethylene-induced hepatotoxicity mediated by CYP2E1., Doni Hikmat Ramdhan, Michihiro Kamijima, Naoyasu Yamada, Yuki Ito, Yukie Yanagiba, Daichi Nakamura, Ai Okamura, Gaku Ichihara, Toshifumi Aoyama, Frank J Gonzalez, Tamie Nakajima, Toxicology and applied pharmacology, 231, (3) 300 - 7,   2008年09月15日, Cytochrome P450 (CYP) 2E1 was suggested to be the major enzyme involved in trichloroethylene (TRI) metabolism and TRI-induced hepatotoxicity, although the latter molecular mechanism is not fully understood. The involvement of CYP2E1 in TRI-induced hepatotoxicity and its underlying molecular mechanism were studied by comparing hepatotoxicity in cyp2e1+/+ and cyp2e1-/- mice. The mice were exposed by inhalation to 0 (control), 1000, or 2000 ppm of TRI for 8 h a day, for 7 days, and TRI-hepatotoxicity was assessed by measuring plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histopathology. Urinary metabolites of trichloroethanol and trichloroacetic acid (TCA) were considerably greater in cyp2e1+/+ compared to cyp2e1-/- mice, suggesting that CYP2E1 is the major P450 involved in the formation of these metabolites. Consistent with elevated plasma ALT and AST activities, cyp2e1+/+ mice in the 2000 ppm group showed histopathological inflammation. TRI significantly upregulated PPARalpha, which might function to inhibit NFkappaB p50 and p65 signalling. In addition, TRI-induced NFkappaB p52 mRNA, and significantly positive correlation between NFkappaB p52 mRNA expression and plasma ALT activity levels were observed, suggesting the involvement of p52 in liver inflammation. Taken together, the current study directly demonstrates that CYP2E1 was the major P450 involved in the first step of the TRI metabolism, and the metabolites produced may have two opposing roles: one inducing hepatotoxicity and the other protecting against the toxicity. Intermediate metabolite(s) from TRI to chloral hydrate produced by CYP2E1-mediated oxidation may be involved in the former, and TCA in the latter.
  • Association of serum NOxlevel with clustering of metabolic syndrome components in middle-aged and elderly general populations in Japan, Ueyama J, Kondo T, Imai R, Kimata A, Yamamoto K, Suzuki K, Inoue T, Ito Y, Miyamoto K.-I, Hasegawa T, Hamajima N, Environmental Health and Preventive Medicine, 13, (1) 36 - 42,   2008年, 査読有り
  • PPAR alpha- and DEHP-induced cancers., Ito Y, Nakajima T, PPAR Res, 2008: 759716,   2008年
  • Molecular mechanics and molecular orbital simulations on specific interactions between peroxisome proliferator-activated receptor PPARalpha and plasticizer., Nakagawa T, Kurita N, Kozakai S, Iwabuchi S, Yamaguchi Y, Hayakawa M, Ito Y, Aoyama T, Nakajima T, J Mol Graph Model, 27(1): 45-58,   2008年
  • Permethrin may induce adult male mouse reproductive toxicity due to cis isomer not trans isomer., Zhang SY, Ueyama J, Ito Y, Yanagiba Y, Okamura A, Kamijima M, Nakajima T, Toxicology, 248(2-3): 136-41,   2008年
  • Different mechanisms of DEHP-induced hepatocellular adenoma tumorigenesis in wild-type and Ppar alpha-null mice., Takashima K, Ito Y, Gonzalez FJ, Nakajima T, J Occup Health, 50(2): 169-80,   2008年
  • Trichloroethylene causes generalized hypersensitivity skin disorders complicated by hepatitis., Kamijima M, Wang H, Huang H, Li L, Shibata E, Lin B, Sakai K, Liu H, Tsuchiyama F, Chen J, Okamura A, Huang X, Hisanaga N, Huang Z, Ito Y, Takeuchi Y, Nakajima T, J Occup Health, 50(4): 328-38,   2008年
  • Styrene trimer may increase thyroid hormone levels via down-regulation of the aryl hydrocarbon receptor (AhR) target gene UDP-glucuronosyltransferase., Yanagiba Y, Ito Y, Yamanoshita O, Zhang SY, Watanabe G, Taya K, Li CM, Inotsume Y, Kamijima M, Gonzalez FJ, Nakajima T, Environ Health Perspect, 116(6): 740-5,   2008年
  • Pyrene-induced CYP1A2 and SULT1A1 may be regulated by CAR and not by AhR, Chul-Ho Lee, Yuki Ito, Yukie Yanagiba, Osamu Yamanoshita, Heon Kim, Shu-Yun Zhang, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGY, 238, (2-3) 147 - 156,   2007年09月, Aryl hydrocarbon receptor (AhR) plays important roles in the regulation and induction of xenobiotic-metabolizing enzymes including the cytochromes P450 1 family (CYP1) and UDP-glucuronosyltransferases 1A (UGT1As) by polycyclic aromatic hydrocarbons as well as chlorinated aromatic hydrocarbons. To determine whether pyrene-induced xenobiotic-metabolizing enzymes are regulated by AhR, male AhR (+/+) and (-/-) mice were used. Both genotyped mice were exposed to 0, 205, 300 or 410 mg/(kg day pyrene), once daily, for four consecutive days by gavage. Exposure to pyrene did not influence hepatic CYP1A1-mRNA in mice of both genotypes, whereas it induced hepatic CYP1A2 protein and mRNA expression and associated 7-ethoxyresorufin O-deethylase and pyrene 1-hydroxylation activities in both AhR (+/+) and (-/-) mice. Similar effects were also found with sulfotransferase 1A1 expression and the associated 1-hydroxypyrene sulfation activity. In contrast, pyrene exposure increased expression of the UGT1A1 and 1A6, and glucuronidation activities associated with 1-hydroxypyrene and 1-naphthol in the liver only in AhR (-/-) mice, although pyrene treatment dose-dependently decreased the latter activity. Pyrene exposure did not increase AhR-mRNA expression in AhR (+/+) mice. In contrast, pyrene-induced expression of the hepatic constitutive androstane receptor (CAR) and one of its target genes, CYP2B10, in both AhR (+/+) and (-/-) mice. These results strongly suggest that pyrene-induced CYP1A2 and SULT1A1 are regulated by CAR, not by AhR. However, the mechanisms of UGT1A1 and 1A6 induction by pyrene were not elucidated in this study. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Pyrene-induced CYP1A2 and SULT1A1 may be regulated by CAR and not by AhR, Chul-Ho Lee, Yuki Ito, Yukie Yanagiba, Osamu Yamanoshita, Heon Kim, Shu-Yun Zhang, Michihiro Kamijima, Frank J. Gonzalez, Tamie Nakajima, TOXICOLOGY, 238, (2-3) 147 - 156,   2007年09月, Aryl hydrocarbon receptor (AhR) plays important roles in the regulation and induction of xenobiotic-metabolizing enzymes including the cytochromes P450 1 family (CYP1) and UDP-glucuronosyltransferases 1A (UGT1As) by polycyclic aromatic hydrocarbons as well as chlorinated aromatic hydrocarbons. To determine whether pyrene-induced xenobiotic-metabolizing enzymes are regulated by AhR, male AhR (+/+) and (-/-) mice were used. Both genotyped mice were exposed to 0, 205, 300 or 410 mg/(kg day pyrene), once daily, for four consecutive days by gavage. Exposure to pyrene did not influence hepatic CYP1A1-mRNA in mice of both genotypes, whereas it induced hepatic CYP1A2 protein and mRNA expression and associated 7-ethoxyresorufin O-deethylase and pyrene 1-hydroxylation activities in both AhR (+/+) and (-/-) mice. Similar effects were also found with sulfotransferase 1A1 expression and the associated 1-hydroxypyrene sulfation activity. In contrast, pyrene exposure increased expression of the UGT1A1 and 1A6, and glucuronidation activities associated with 1-hydroxypyrene and 1-naphthol in the liver only in AhR (-/-) mice, although pyrene treatment dose-dependently decreased the latter activity. Pyrene exposure did not increase AhR-mRNA expression in AhR (+/+) mice. In contrast, pyrene-induced expression of the hepatic constitutive androstane receptor (CAR) and one of its target genes, CYP2B10, in both AhR (+/+) and (-/-) mice. These results strongly suggest that pyrene-induced CYP1A2 and SULT1A1 are regulated by CAR, not by AhR. However, the mechanisms of UGT1A1 and 1A6 induction by pyrene were not elucidated in this study. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Association of a polymorphism in the ornithine decarboxylase gene with whole blood polyamine concentrations in a non-smoking healthy population, Takaaki Kondo, Nobuyuki Hamajima, Kazuko Nishio, Yoshiko Ishida, Ryota Imai, Jun Ueyama, Shoko Torita, Yurie Kasai, Ryoko Yamamoto, Koji Suzuki, Yoshinori Ito, JOURNAL OF HEALTH SCIENCE, 53, (4) 406 - 412,   2007年08月, 査読有り, Ornithine decarboxylase (ODC) is the rate-limiting key enzyme in the biosynthesis of polyamines which have been confirmed to possess potent antioxidant and antiglycating properties. The aim of the present study was to examine the relationship of the ODC polymorphism and circulating whole blood polyamine concentrations. The study subjects were non-smoking, healthy men (n = 30) and women (n = 30) aged 55-69 years with equal numbers of AA, GA, and GG genotypes of the ODC gene, who were randomly recruited from 607 health checkup examinees. The whole blood polyamines (spermidine and spermine) were determined by high-performance liquid chromatography and were adjusted for hematocrit. The difference in the adjusted polyamines across the ODC gene was statistically tested using analysis of covariance. Women homozygous for the A-allele showed significantly higher spermidine levels than those with other genotypes. No such association was found among men, and spermine showed no association with the ODC genotype. In conclusion, the ODC polymorphism is significantly associated with whole blood polyamines in women. The ODC gene seems to be expressed more actively among female A-allele homozygotes than women carrying the G-allele.
  • Permethrin may disrupt testosterone biosynthesis via mitochondrial membrane damage of leydig cells in adult male mouse, Shu-Yun Zhang, Yuki Ito, Osamu Yamanoshita, Yukie Yanagiba, Miya Kobayashi, Kazuyoshi Taya, ChunMei Li, Ai Okamura, Maiko Miyata, Jun Ueyama, Chul-Ho Lee, Michihiro Kamijima, Tamie Nakajima, ENDOCRINOLOGY, 148, (8) 3941 - 3949,   2007年08月, Permethrin, a popular synthetic pyrethroid insecticide used to control noxious insects in agriculture, forestry, households, horticulture, and public health throughout the world, poses risks of environmental exposure. Here we evaluate the reproductive toxicity of cis-permethrin in adult male ICR mice that were orally administered cis- permethrin ( 0, 35, or 70 mg/kg center dot d) for 6 wk. Caudal epididymal sperm count and sperm motility in the treated groups were statistically reduced in a dose-dependent manner. Testicular testosterone production and plasma testosterone concentration were significantly and dose-dependently decreased with an increase in LH, and a significant regression was observed between testosterone levels and cis-permethrin residues in individual mice testes after exposure. However, no significant changes were observed in body weight, reproductive organ absolute and relative weights, sperm morphology, and plasma FSH concentration after cis- permethrin treatment. Moreover, cis- permethrin exposure significantly diminished the testicular mitochondrial mRNA expression levels of peripheral benzodiazepine receptor (PBR), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side- chain cleavage (P450scc) and enzyme and protein expression levels of StAR and P450scc. At the electron microscopic level, mitochondrial membrane damage was found in Leydig cells of the exposed mouse testis. Our results suggest that the insecticide permethrin may cause mitochondrial membrane impairment in Leydig cells and disrupt testosterone biosynthesis by diminishing the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone in the cells, thus reducing subsequent testosterone production.
  • Di(2-ethylhexyl)phthalate induces hepatic tumorigenesis through a peroxisome proliferator-activated receptor alpha-independent pathway., Yuki Ito, Osamu Yamanoshita, Nobuyuki Asaeda, Yoshiaki Tagawa, Chul-Ho Lee, Toshifumi Aoyama, Gaku Ichihara, Koichi Furuhashi, Michihiro Kamijima, Frank J Gonzalez, Tamie Nakajima, Journal of occupational health, 49, (3) 172 - 82,   2007年05月, Di(2-ethylhexyl)phthalate (DEHP), a commonly used industrial plasticizer, causes liver tumorigenesis presumably via activation of peroxisome proliferator-activated receptor alpha (PPARalpha). The mechanism of DEHP tumorigenesis has not been fully elucidated, and to clarify whether DEHP tumorigenesis is induced via PPARalpha, we compared DEHP-induced tumorigenesis in wild-type and Pparalpha-null mice. Mice of each genotype were divided into three groups, and treated for 22 months with diets containing 0, 0.01 or 0.05% DEHP. Surprisingly, the incidence of liver tumors was higher in Pparalpha-null mice exposed to 0.05% DEHP (25.8%) than in similarly exposed wild-type mice (10.0%). These results suggest the existence of pathways for DEHP-induced hepatic tumorigenesis that are independent of PPARalpha. The levels of 8-OHdG increased dose-dependently in mice of both genotypes, but the degree of increase was higher in Pparalpha-null than in wild-type mice. NFkappaB levels also significantly increased in a dose-dependent manner in Pparalpha-null mice. The protooncogene c-jun-mRNA was induced, and c-fos-mRNA tended to be induced only in Pparalpha-null mice fed a 0.05% DEHP-containing diet. These results suggest that increases in oxidative stress induced by DEHP exposure may lead to the induction of inflammation and/or the expression of protooncogenes, resulting in a high incidence of tumorigenesis in Pparalpha-null mice.
  • Induction of peroxisome proliferator-activated receptor alpha (PPAR alpha)-related enzymes by di(2-ethylhexyl) phthalate (DEHP) treatment in mice and rats, but not marmosets, Yuki Ito, Osamu Yamanoshita, Yoshimasa Kurata, Michihiro Kamijima, Toshifumi Aoyama, Tamie Nakajima, ARCHIVES OF TOXICOLOGY, 81, (3) 219 - 226,   2007年03月, To clarify species differences in the induction of peroxisome proliferator-activated receptor alpha (PPAR alpha)-related enzymes by di(2-ethylhexyl)phthalate (DEHP) exposure, we investigated the inductions of PPAR alpha and its target genes (mitochondrial medium-chain acyl-CoA dehydrogenase (MCAD) and peroxisomal keto-acyl-CoA thiolase (PT) in liver from mice (CD-1), rats (Sprague-Dawley), and marmosets (Callithrix jacchus) exposed to DEHP. Male mice and rats were treated with 0, 1.25 and 2.5 mmol/kg DEHP for 2 weeks, and marmosets with 0, 0.25, 1.25 and 6.25 mmol/kg DEHP for 15 months by gavage. Hepatic mono(2-ethylhexyl)phthalate (MEHP) levels were significantly higher in mice and rats than in marmosets. The constitutive expression of hepatic PPAR alpha was 5-7 times greater in rats and mice than in marmosets, but DEHP treatment did not induce PPAR alpha-mRNA in all animals. The treatment-induced PT expression detected either by anti-PT antibody or PT-mRNA levels in the liver only from mice and rats, and the induction of the mRNA was greater in the latter than in the former. Thus, DEHP used in this experiment influenced the peroxisomal enzymes in mice and rats, but did not affect the mitochondrial enzymes in any animals or the peroxisomal enzymes in marmosets. These results suggest that there are species differences in the induction of PPAR alpha-related enzymes, especially in peroxisomal enzymes by DEHP treatment, and their underlying mechanism may in part reside in the different constitutive levels of PPAR alpha and different forming levels of MEHP.
  • Peroxisome proliferator-activated receptor alpha protects against glomerulonephritis induced by long-term exposure to the plasticizer di-(2-ethylhexyl)phthalate, Yuji Kamijo, Kazuhiko Hora, Tarnie Nakajima, Keiichi Kono, Kyoko Takahashi, Yuki Ito, Makoto Higuchi, Kendo Kiyosawa, Hidekazu Shigematsu, Frank J. Gonzalez, Toshifumi Aoyama, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 18, (1) 176 - 188,   2007年01月, Safety concerns about di-(2-ethylhexyl)phthalate (DEHP), a plasticizer and a probable endocrine disruptor, have attracted considerable public attention, but there are few studies about long-term exposure to DEHP. DEHP toxicity is thought to involve peroxisome proliferator-activated receptor a (PPAR alpha), but this contention remains controversial. For investigation of the long-term toxicity of DEHP and determination of whether PPAR alpha mediates toxicity, wild-type and PPAR alpha-null mice were fed a diet that contained 0.05 or 0.01% DEHP for 22 mo. PPAR alpha-null mice that were exposed to DEHP exhibited prominent immune complex glomerulortephritis, most likely related to elevated glomerular oxidative stress. Elevated NADPH oxidase, low antioxidant enzymes, and absence of the PPAR alpha-dependent anti-inflammatory effects that normally antagonize the NF kappa B signaling pathway accompanied the glomerulonephritis in PPAR alpha-null mice. The results reported here indicate that PPAR alpha protects against the nephrotoxic effects of long-term exposure to DEHP.
  • PPARと環境汚染物質の毒性―DEHPによるPPARαを介した生殖・発生毒性, 森谷隆, 伊藤由起, 那須民江, 医学のあゆみ, 220, (1) 125 - 130,   2007年, 招待有り
  • Association of abdominal circumference with serum nitric oxide concentration in healthy population, Kondo T, Ueyama J, Imai R, Suzuki K, Ito Y, Environmental Health and Preventive Medicine, 11, (6) 321 - 325,   2006年, 査読有り
  • Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets., Yuki Ito, Hiroshi Yokota, Ruisheng Wang, Osamu Yamanoshita, Gaku Ichihara, Hailan Wang, Yoshimasa Kurata, Kenji Takagi, Tamie Nakajima, Archives of toxicology, 79, (3) 147 - 54,   2005年03月, To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague-Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP) from DEHP, differed by 27- to 357-fold among species; the activity was highest in the small intestines of mice and lowest in the lungs of marmosets. This might be because of the significant differences between Vmax/Km values of lipase for DEHP among the species. UGT activity for MEHP in the liver microsomes was highest in mice, followed by rats and marmosets. These differences, however, were only marginal compared with those for lipase activity. ADH and ALDH activity also differed among species; the activity of the former in the livers of marmosets was 1.6-3.9 times greater than in those of rats or mice; the activity of the latter was higher in rats and marmosets (2-14 times) than in mice. These results were quite different from those for lipase or UGT activity. Because MEHP is considered to be the more potent ligand to peroxisome proliferator-activated receptor alpha involved in different toxic processes, a possibly major difference in MEHP-formation capacity could be also considered on extrapolation from rodents to humans.
  • A review of hazardous chemical toxicity studies utilizing genetically-modified animals--their applications for risk assessment., Nakajima T, Wang RS, Ito Y, Aoyama T, Kamijima M, Ind Health, 43: 615-622, (4) 615 - 22,   2005年
  • Simultaneous determination of water-soluble vitamins in a vitamin-enriched drink by an in-capillary enzyme reaction method, H Okamoto, T Nakajima, Y Ito, JOURNAL OF CHROMATOGRAPHY A, 986, (1) 153 - 161,   2003年01月, 査読有り, The in-capillary enzyme reaction method was used to determine riboflavin phosphate in a vitamin-enriched drink based on its conversion to riboflavin (vitamin B,) with alkaline phosphatase. Simultaneously, three water-soluble vitamins [thiamine nitrate (vitamin B, mononitrate), pyridoxine hydrochloride (vitamin B, hydrochloride) and nicotinamide (vitamin PP)] and anhydrous caffeine in the drink were subjected to quantitative analysis. In the system, electrophoretic migration was used to mix zones containing the substrate (riboflavin phosphate) and the enzyme (alkaline phosphatase). The reaction was then allowed to proceed in the presence of a weak electric field and, finally, the product (riboflavin) of enzyme reaction and other water-soluble vitamins migrated under the influence of an applied electric field to the detector. All the active ingredients and the formulation excipients were successfully separated by micellar electrokinetic chromatography with 135 mM sodium dodecyl sulfate. To prevent inhibition of enzyme reaction by the addition of sodium dodecyl sulfate to the reaction zone, sandwich mode injection, in which plugs of sandwich solution without sodium dodecyl sulfate were introduced into the capillary on both sides of the reaction zone, was utilized as a barrier to protect the enzyme reaction from the inhibitor. The relationship between the peak area of the product and the concentration of the substrate was calculated in the in-capillary enzyme reaction method. Excellent linearity was obtained, with correlation coefficients of 0.9999. The established method was validated and demonstrated to be applicable to the determination of the five active ingredients, including riboflavin phosphate, in a commercial vitamin-enriched drink. No interference from the formulation excipients was observed. Good linearities were obtained, with correlation coefficients above 0.999. Recoveries and precisions ranged from 99.3 to 101.8%, and from 0.1 to 2.5% RSD, respectively. Good agreement was obtained between the established method and traditional high-performance liquid chromatographic methods. These results suggest that the in-capillary enzyme reaction method can be used for the simultaneous determination of riboflavin phosphate and other water-soluble vitamins in pharmaceuticals. (C) 2002 Elsevier Science B.V. All rights reserved.

MISC

  • 1.5歳児および3歳児における使い捨ておむつを用いた殺虫剤の曝露量評価, 大矢 奈穂子, 伊藤 由起, 榎原 毅, 佐藤 博貴, 日置 啓介, 上山 純, 加藤 沙耶香, 松木 太郎, 杉浦 真弓, 齋藤 伸治, 上島 通浩, 東海公衆衛生雑誌, 7, (1) 37 - 37,   2019年07月
  • 陰膳調査における女子大学生の食事摂取状況について, 野正 夏鈴, 大矢 奈穂子, 伊藤 由起, 佐藤 博貴, 北森 一哉, 大島 志織, 峰松 明也子, 湊 京子, 榎原 毅, 上島 通浩, 東海公衆衛生雑誌, 7, (1) 47 - 47,   2019年07月
  • 神経発達期における縦断的な有機リン系殺虫剤曝露評価, 大矢 奈穂子, 伊藤 由起, 榎原 毅, 佐藤 博貴, 日置 啓介, 上山 純, 加藤 沙耶香, 松木 太郎, 杉浦 真弓, 齋藤 伸治, 上島 通浩, 産業衛生学雑誌, 61, (2) 78 - 78,   2019年03月
  • 非線形回帰モデルによる有機リン系殺虫剤尿中代謝物のリスク評価 急性毒性の異なる薬剤間での比較検討, 佐藤 博貴, 伊藤 由起, 文堂 生深, 花井 ちなみ, 西村 正也, 上山 純, 上島 通浩, 産業衛生学雑誌, 61, (2) 78 - 78,   2019年03月
  • 2-エチル-1-ヘキサノール吸入曝露中止後のマウス嗅上皮の構造変化と炎症細胞浸潤, 三宅 美緒, 伊藤 由起, 大矢 奈穂子, 佐藤 博貴, 若山 貴成, 上島 通浩, 産業衛生学雑誌, 61, (2) 78 - 78,   2019年03月
  • 1歳半児におけるジノテフラン曝露量と生活環境および食意識との関連, 大矢 奈穂子, 伊藤 由起, 上山 純, 加藤 沙耶香, 松木 太郎, 佐藤 博貴, 齋藤 伸治, 杉浦 真弓, 榎原 毅, 上島 通浩, 日本衛生学雑誌, 74, (Suppl.) S122 - S122,   2019年02月
  • 一目で分かる!専門用語:室内空気汚染分野, 若山貴成, 伊藤由起, 上島通浩, ビルと環境, 163,   2018年12月, 招待有り
  • エコチル調査愛知ユニットセンターにおける参加児の質問票の回収状況と発達について, 加藤沙耶香, 加藤沙耶香, 榎原毅, 榎原毅, 松木太郎, 松木太郎, 伊藤由起, 伊藤由起, 杉浦真弓, 杉浦真弓, 齋藤伸治, 齋藤伸治, 上島通浩, 上島通浩, 東海公衆衛生雑誌, 6,   2018年07月07日
  • 2‐エチル‐1‐ヘキサノール吸入曝露後のマウス肝臓の脂質解析, 若山貴成, 若山貴成, 伊藤由起, 三宅美緒, 酒井潔, 大矢奈穂子, 佐藤博貴, 大野浩之, 上島通浩, 産業衛生学雑誌, 60,   2018年05月16日
  • 2‐エチル‐1‐ヘキサノール慢性吸入曝露による嗅上皮の病理変化と嗅覚試験への影響, 三宅美緒, 伊藤由起, 大矢奈穂子, 佐藤博貴, 若山貴成, 上島通浩, 産業衛生学雑誌, 60,   2018年05月16日
  • 2‐エチル‐1‐ヘキサノール慢性吸入曝露とうつ様行動との関係, 伊藤由起, 三宅美緒, 大矢奈穂子, 佐藤博貴, 若山貴成, 若山貴成, 上島通浩, 産業衛生学雑誌, 60,   2018年05月16日
  • DDVP投与Wistarラットにおけるコリンエステラーゼ活性と尿中代謝物の非線形モデル解析, 佐藤博貴, 伊藤由起, 花井ちなみ, 西村正也, 上山純, 上島通浩, 産業衛生学雑誌, 60,   2018年05月16日
  • バイオモニタリング手法を用いた日本人小児ピレスロイド系殺虫剤曝露レベルの国際比較, 上山 純, 上田 裕子, 伊藤 由起, 榎原 毅, 大矢 奈穂子, 加藤 沙耶香, 小栗 朋子, 庄司 直人, 齋藤 伸治, 上島 通浩, 日本衛生学雑誌, 73, (Suppl.) S280 - S280,   2018年03月
  • トリクロロエチレンによる過敏症症候群における曝露濃度と感受性因子の交互作用, 那須 民江, 王 海蘭, 伊藤 由起, 内藤 久雄, 柳場 由絵, 八谷 寛, 上島 通浩, 日本衛生学雑誌, 73, (Suppl.) S276 - S276,   2018年03月
  • 3歳児の尿中有機リン系殺虫剤代謝物濃度と採尿季節の関係, 伊藤 由起, 大矢 奈穂子, 榎原 毅, 佐藤 博貴, 加藤 沙耶香, 上山 純, 庄司 直人, 松木 太郎, 杉浦 真弓, 斎藤 伸治, 上島 通浩, 産業衛生学雑誌, 60, (2) 47 - 47,   2018年03月
  • フェニトロチオンによるラット精子毒性に精巣上体リン脂質症が関与している, 三宅 美緒, 伊藤 由起, 鈴木 日美子, 冨澤 元博, 佐藤 博貴, 劉 明, 岡村 愛, 那須 民江, 大谷 勝巳, 滝野 寿, 稲垣 宏, 上島 通浩, 産業衛生学雑誌, 60, (2) 48 - 48,   2018年03月
  • Wistarラットを用いたジメチル-2,2-ジクロロビニルホスフェイト(DDVP)の影響評価におけるベンチマークドーズ法の適用, 佐藤 博貴, 伊藤 由起, 花井 ちなみ, 上島 通浩, 産業衛生学雑誌, 60, (2) 48 - 48,   2018年03月
  • Wistarラットを用いたDDVP投与によるコリンエステラーゼ活性抑制と尿中代謝物量の関係の検討, 佐藤 博貴, 伊藤 由起, 花井 ちなみ, 西村 正也, 上山 純, 上島 通浩, 産業衛生学雑誌, 60, (2) 55 - 56,   2018年03月
  • 3歳児の尿中有機リン系殺虫剤代謝物濃度と採尿季節の関係, 伊藤 由起, 大矢 奈穂子, 榎原 毅, 佐藤 博貴, 加藤 沙耶香, 上山 純, 庄司 直人, 松木 太郎, 杉浦 真弓, 斎藤 伸治, 上島 通浩, 産業衛生学雑誌, 60, (2) 47 - 47,   2018年03月
  • フェニトロチオンによるラット精子毒性に精巣上体リン脂質症が関与している, 三宅 美緒, 伊藤 由起, 鈴木 日美子, 冨澤 元博, 佐藤 博貴, 劉 明, 岡村 愛, 那須 民江, 大谷 勝巳, 滝野 寿, 稲垣 宏, 上島 通浩, 産業衛生学雑誌, 60, (2) 48 - 48,   2018年03月
  • Wistarラットを用いたジメチル-2,2-ジクロロビニルホスフェイト(DDVP)の影響評価におけるベンチマークドーズ法の適用, 佐藤 博貴, 伊藤 由起, 花井 ちなみ, 上島 通浩, 産業衛生学雑誌, 60, (2) 48 - 48,   2018年03月
  • Wistarラットを用いたDDVP投与によるコリンエステラーゼ活性抑制と尿中代謝物量の関係の検討, 佐藤 博貴, 伊藤 由起, 花井 ちなみ, 西村 正也, 上山 純, 上島 通浩, 産業衛生学雑誌, 60, (2) 55 - 56,   2018年03月
  • トリクロロエチレンによる過敏症症候群における曝露濃度と感受性因子の交互作用, 那須 民江, 王 海蘭, 伊藤 由起, 内藤 久雄, 柳場 由絵, 八谷 寛, 上島 通浩, 日本衛生学雑誌, 73, (Suppl.) S276 - S276,   2018年03月
  • 小児におけるトリクロロエタノールの薬物動態・薬力学の発達・成長に伴う変化の解析, 井上美帆, 糸原光太郎, 佐藤博貴, 加藤祐子, 石井祥代, 伊藤由起, 那須民江, 上島通浩, 矢野育子, 矢野育子, 松原和夫, 佐和貞治, 橋本悟, 臨床薬理, 48, (Supplement) S274 - S274,   2017年11月15日
  • 妊娠の進行に伴う尿中殺虫剤曝露マーカー濃度の変動についての検討, 上島 通浩, 加藤 沙耶香, 小栗 朋子, 庄司 直人, 大矢 奈穂子, 齋藤 伸治, 杉浦 真弓, 榎原 毅, 伊藤 由起, 上山 純, 青井 亜里沙, 山田 泰行, 冨澤 元博, 若林 千鶴子, 宮田 麻衣子, 日本毒性学会学術年会, 44, (0) P - 235,   2017年06月, 妊娠中の低用量殺虫剤曝露による児への健康影響リスクを疫学研究で検討する際、一時点の尿中曝露マーカー濃度をもって胎児期の曝露量とみなせるかには議論がある。このため、妊娠中に二回採取(順にT1, T2)した尿中のマーカー濃度を測定した。出生コホート研究「子どもの健康と環境に関する全国調査(エコチル調査)」への愛知県の参加者で、妊娠20週までにT1採尿を行った者の中から66名(平均31.0±SD5.3歳)を抽出し対象者とした。有機リン(OP)代謝物(4種類のジアルキルリン酸(DAP))、ネオニコチノイド (NN)(アセタミプリド、イミダクロプリド、クロチアニジン、チアメトキサム(TM)、チアクロプリド、ジノテフラン(DN))は高速液体クロマトグラフタンデム質量分析計で、また、ピレスロイド(PY)代謝物(3-フェノキシ安息香酸(PBA)、トランス型クリサンテマムジカルボン酸、ジクロロビニルジメチルシクロプロパンカルボン酸(DCCA))はガスクロマトグラフ質量分析計により測定した。各物質の検出率(%)は、DAP 60-100、NN 1 -75、PY 37-100で、T1(平均14.2週)、T2(同25.2週)ともほぼ同じであった。検出率が6割以上だったDAP、TM、DN、PBA、DCCAについて、T1、T2の濃度を比較した結果、DAPとNNでは有意差がない一方、PY(PBAとDCCA)については有意にT2>T1であった(Wilcoxonの符号付順位検定)。また、三分位点濃度で3群に分けた場合の2回の測定のカッパ係数は、OP、NNでは0.40以下であったが、PYでは中等度の一致(PBA 0.50、DCCA 0.48)を示した。さらに、DAPは20パーセンタイル値、PBA、DCCA、NNについては30パーセンタイル値をカットオフ濃度として対象者を2群に分けた時のカッパ係数は、それぞれ0.49、0.59、0.64、0.45-0.71であった。すなわち、1回の採尿で曝露が相対的に少ない人を明らかにできること、PYのマーカーはOP、NNに比べ集団の曝露評価の変数として安定していることが示唆された。
  • 使い捨てオムツを用いた尿中ネオニコチノイド系殺虫剤のバイオモニタリング手法の開発と小児への実践応用, 上山 純, 青井 亜里沙, 伊藤 由起, 榎原 毅, 大矢 奈穂子, 加藤 沙耶香, 小栗 朋子, 庄司 直人, 佐藤 博貴, 三宅 美緒, 上島 通浩, The Journal of Toxicological Sciences, 42, (Suppl.) S258 - S258,   2017年06月
  • 使い捨てオムツを用いた尿中ネオニコチノイド系殺虫剤のバイオモニタリング手法の開発と小児への実践応用, 上山 純, 青井 亜里沙, 伊藤 由起, 榎原 毅, 大矢 奈穂子, 加藤 沙耶香, 小栗 朋子, 庄司 直人, 佐藤 博貴, 三宅 美緒, 上島 通浩, 日本毒性学会学術年会, 44, (0) P - 99,   2017年06月, ネオニコチノイド系殺虫剤(NEO)は農林業や一般家庭で汎用されている殺虫剤であり、ヒトへの曝露状況調査が必要な物質の一つである。ヒトの尿を用いた生物学的モニタリングは、化学物質曝露評価手法の一つとして使用されてきたが、採尿が難しいオムツ着用者を対象とした調査は進んでいない。本研究では、簡便な採尿方法として使い捨て紙オムツを用いた尿中NEO濃度測定法(オムツ法)の確立を目指した。対象物質は6種のNEO (acetamiprid, imidacloprid, thiacloprid, thiamethoxam, clothianidinおよびdinotefuran)、acetamiprid代謝物である<i>N</i>-desmethylacetamipridの計7種類とした。使用済み紙オムツから尿をアセトン抽出し、多孔性珪藻土カラムおよび逆相系固相カラムにて精製した後に液体クロマトグラフ-タンデム型質量分析計(LC-MS/MS)で分離定量分析を行った。既知濃度尿のオムツへの添加実験によってNEOの絶対回収率は41から100%と算出された。検量線はいずれもr<sup>2</sup> = 0.988以上と良好な直線性を示した(濃度範囲1.25-20 µg/L)。日内変動および日間変動の相対標準偏差(%RSD)は、それぞれ3.3-12.7%および4.3-19.5%であった。検出下限値は0.5 (acetamiprid)、1.9 (imidacloprid)、0.9 (thiacloprid)、2.8 (thiamethoxam)、3.6 (clothianidin)、2.3 (dinotefuran)、0.4 µg/L (<i>N</i>-desmethylacetamiprid)と算出された。50人の3歳児から使用済み紙オムツを収集して分析した結果、検出率は74%のdinotefuranと68%の<i>N</i>-desmethylacetamipridで高く、その他は10% (acetamiprid), 4% (imidacloprid), 2% (thiacloprid), 12% (thiamethoxam), 28% (clothianidin)であった。オムツ法の検出下限値は、尿を直接分析する既報のそれに比べて高いが、使用済み紙オムツからNEOを検出できることが証明された。今後は本測定法を用いて、子どものNEO曝露状況の詳細な調査を進める予定である。
  • 2‐エチル‐1‐ヘキサノール吸入曝露中止後のマウス嗅上皮回復の病理学的解析, 三宅美緒, 伊藤由起, 大矢奈穂子, 佐藤博貴, 若山貴成, 上島通浩, 日本産業衛生学会講演集(CD-ROM), 90th,   2017年05月
  • 殺虫剤散布作業・関連業務従事者の薬剤使用品目および尿中代謝物量の変遷, 佐藤博貴, 上山純, 伊藤由起, 五藤雅博, 三宅美緒, 大矢奈穂子, 近藤高明, 齋藤勲, 柴田英治, 上島通浩, 日本産業衛生学会講演集(CD-ROM), 90th,   2017年05月
  • ガスクロマトグラフ質量分析計(GC-MS)と液体クロマトグラフタンデム型質量分析計(LC-MS/MS)を併用した血清中トリクロホスおよび代謝物の同時測定法の開発, 佐藤 博貴, 伊藤 由起, 井上 美帆, 中平 有紀, 橋本 悟, 上島 通浩, 産業衛生学雑誌, 59, (1) 48 - 48,   2017年01月
  • 尿中有機リン系殺虫剤代謝物測定の個人間変動と施設間差についての検討, 伊藤由起, 上山純, 中山祥嗣, 磯部友彦, 佐藤博貴, 大矢奈穂子, 仲井邦彦, 上島通浩, 日本衛生学雑誌(Web), 71, (Supplement) S213 - S213,   2016年05月
  • トリクロロエチレンによるHypersensitivity 患者の曝露濃度から許容濃度再考の必要性を考察する, 那須 民江, 王 棟, 王 海蘭, 山ノ下 理, 伊藤 由起, 内藤 久雄, 上島 通浩, 産業衛生学雑誌, 58, (臨増) 419 - 419,   2016年05月
  • 有機リン系殺虫剤分解酵素活性と尿中代謝物の関連, 佐藤博貴, 伊藤由起, 上山純, 加納裕也, 荒川朋弥, 五藤雅博, 近藤高明, 杉浦友香, 斎藤勲, 柴田英治, 上島通浩, 産業衛生学雑誌, 58, (1) 39 - 39,   2016年01月20日
  • トリクロロエチレン曝露量とHLA遺伝型に対する皮膚過敏症への影響, 山ノ下 理, 上島 通浩, 王 海蘭, 伊藤 由起, 内藤 久雄, 那須 民江, 産業衛生学雑誌, 58, (1) 38 - 39,   2016年01月
  • トリクロロエチレンによるHypersensitivity 15年間の日中共同研究による患者の曝露濃度推移の考察, 那須 民江, 王 棟, 王 海蘭, 山ノ下 理, 伊藤 由起, 内藤 久雄, 上島 通浩, 産業衛生学雑誌, 58, (1) 39 - 39,   2016年01月
  • 尿中有機リン系殺虫剤代謝物測定の施設間,個人間変動についての検討, 伊藤由起, 上山純, 中山祥嗣, 磯部友彦, 佐藤博貴, 仲井邦彦, 上島通浩, 産業衛生学雑誌, 57, (6) 329 - 329,   2015年11月20日
  • 尿中有機リン系殺虫剤代謝物測定の施設間、個人間変動についての検討, 伊藤 由起, 上山 純, 中山 祥嗣, 磯部 友彦, 佐藤 博貴, 仲井 邦彦, 上島 通浩, 産業衛生学雑誌, 57, (6) 329 - 329,   2015年11月
  • 有機リン系殺虫剤散布作業者におけるパラオキソナーゼ1酵素活性と尿中代謝物濃度の関連, 佐藤博貴, 伊藤由起, 上山純, 五藤雅博, 近藤高明, 杉浦友香, 柴田英治, 上島通浩, 日本産業衛生学会講演集(CD-ROM), 88th, (臨増) 257 - 257,   2015年05月13日
  • 殺虫剤散布作業従事者におけるParaoxonase 1遺伝子多型と尿中代謝物の関係, 佐藤博貴, 伊藤由起, 上山純, 加納裕也, 荒川朋弥, 五藤雅博, 近藤高明, 杉浦友香, 斎藤勲, 柴田英治, 上島通浩, 産業衛生学雑誌, 57, (2) 62 - 62,   2015年03月20日
  • 有機リン系殺虫剤曝露者における尿中代謝物濃度および代謝酵素活性の関連について, 佐藤博貴, 伊藤由起, 上山純, 加納裕也, 荒川朋弥, 五藤雅博, 近藤高明, 杉浦友香, 斎藤勲, 柴田英治, 上島通浩, 産業衛生学雑誌, 57, (2) 51 - 51,   2015年03月20日
  • フェニトロチオンとその主要代謝物投与による雄性ラット副生殖器への影響, 三宅美緒, 伊藤由起, 佐藤博貴, 大谷勝己, 榎原毅, 上島通浩, 日本衛生学雑誌, 70, (Supplement) S206 - S206,   2015年03月
  • 害虫防除作業者における,殺虫剤解毒作用へのパラオキソナーゼ1遺伝子多型の影響, 佐藤博貴, 伊藤由起, 荒川朋弥, 加納裕也, 上山純, 五藤雅博, 柴田英治, 近藤高明, 斎藤勲, 上島通浩, 日本産業衛生学会講演集(CD-ROM), 87th, (臨増) 594 - 594,   2014年05月01日
  • トリクロロエチレンによる重症皮膚肝障害の個体感受性マーカーの解析, 山ノ下理, 内藤久雄, 伊藤由起, 王海蘭, 黄漢林, 上島通浩, 那須民江, 日本産業衛生学会講演集(CD-ROM), 87th,   2014年05月01日
  • トリクロロエタノールの代謝におけるCYP2E1の役割, 日比野優衣, 内藤久雄, 王棟, 伊藤由起, 上島通浩, 那須民江, 産業衛生学雑誌, 55,   2013年03月20日
  • トリクロロエチレンとその代謝物のHypersensitivityに関する検討, 日比野優衣, 内藤久雄, 王棟, 趙娜, 宋向栄, 王海蘭, 伊藤由起, 上島通浩, 那須民江, 日本衛生学雑誌, 68,   2013年03月
  • 胎生期フタル酸ジ‐2‐エチルヘキシル曝露がレプチンに及ぼす影響, 林由美, 伊藤由起, 内藤久雄, 近藤高明, 上島通浩, 那須民江, 日本内分泌かく乱化学物質学会研究発表会要旨集, 15th,   2012年12月18日
  • 胎生期DEHP曝露による低栄養と摂食行動, 林由美, 伊藤由起, 内藤久雄, 王棟, 賈小芳, 田川雅大, 上島通浩, 那須民江, 日本衛生学雑誌, 67,   2012年02月17日
  • ヒトPPARαトランスジェニックマウスを用いたDEHPの肝発がん性評価, 伊藤由起, 柳場由絵, 林由美, 内藤久雄, 三宅美緒, 上島通浩, 那須民江, 日本産業衛生学会講演集(CD-ROM), 85th,   2012年
  • PPARαとDEHPの動態に関する研究, 田川雅大, 林由美, 山岸希, 中島亮輔, 伊藤由起, 内藤久雄, 那須民江, 日本衛生学雑誌, 66,   2011年02月15日
  • ヒトPPARαトランスジェニックマウスを用いたDEHPの発がん性評価, 伊藤由起, ドニヒクマット ラムダン, 柳場由絵, 林由美, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌, 66,   2011年02月15日
  • DEHP曝露の雌雄マウス生殖器への影響, 山岸希, 林由美, 王棟, 伊藤由起, DONI HIKMAT Ramdhan, 内藤久雄, 那須民江, 日本衛生学雑誌, 66,   2011年02月15日
  • 妊娠期DEHP曝露による母獣の血漿中トリグリセライド減少メカニズム, 林由美, 山岸希, 伊藤由起, 内藤久雄, 那須民江, 日本衛生学雑誌, 66,   2011年02月15日
  • APFOはPPARαに関連したテストステロンの低下を招くかもしれない, 李 宇飛, ラムダン・ドニヒクマット, 伊藤 由起, 林 由美, 柳場 由絵, 岡村 愛, 山岸 希, 玉田 葉月, ゴンザレス・フランク, 那須 民江, 日本衛生学雑誌, 66, (2) 480 - 480,   2011年02月
  • 一般生活者集団における子どもとその親の尿中殺虫剤代謝物濃度の比較, 王棟, 上島通浩, 上山純, 内藤久雄, 伊藤由起, 那須民江, 日本産業衛生学会講演集(CD-ROM), 84th,   2011年
  • DEHP曝露によるPPARαの活性化で妊娠マウスの血漿中必須脂肪酸濃度が低下する, 中島亮輔, 林由美, 玉棟, 伊藤由起, RAMDHAN Doni Hikat, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌, 65,   2010年04月15日
  • 可塑剤の毒性発現にはPPARαのみならずCARも関与しているかもしれない, 伊藤由起, 柳場由絵, RAMDHAN Doni Hikmat, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌, 65,   2010年04月15日
  • 胎生期DEHP曝露による低栄養と生活習慣病リスクとの関連, 林由美, 伊藤由起, 柳場由絵, 王棟, 山岸希, 賈小芳, 内藤久雄, 那須民江, 日本衛生学雑誌, 65,   2010年04月15日
  • ディーゼル排気ナノ粒子の海馬ステロイド合成系への影響, 山岸希, 伊藤由起, RAMDHAN Doni Hikmat, 柳場由絵, 林由美, 内藤久雄, 鈴木明, 井上健一郎, 那須民江, 日本衛生学雑誌, 65,   2010年04月15日
  • パーフルオロオクタン酸による肝障害とPPARalphaの関与に関する研究, 那須 民江, 中川 智彦, Hikmat Ramdhan Doni, 内藤 久雄, 玉田 葉月, 伊藤 由起, 林 由美, 山岸 希, 柳場 由絵, 日本衛生学雑誌, 65, (2) 361 - 361,   2010年04月
  • 妊娠マウスのDEHP曝露はPPARαを介して母獣血漿中必須脂肪酸濃度を低下させる, 中島亮輔, 林由美, 王棟, 伊藤由起, HIKMAT Ramdhan Doni, 内藤久雄, 上島通浩, 那須民江, 産業衛生学雑誌, 52,   2010年01月20日
  • 妊娠マウスのDEHP曝露はPPARαを介して胎仔・新生仔の生存に影響を与える, 林由美, 伊藤由起, 王棟, 柳場由絵, 山岸希, 玉田葉月, HIKMATL Ramdhan Doni, 内藤久雄, 那須民江, 産業衛生学雑誌, 52, (1) 58 - 59,   2010年01月20日
  • 核内受容体PPARαによるフタル酸ジ2-エチルヘキシルの生殖・次世代影響の制御, 林 由美, 伊藤 由起, 玉田 葉月, 山岸 希, 柳場 由絵, 王 棟, 上島 通浩, 那須 民江, 日本衛生学雑誌, 64, (2) 359 - 359,   2009年03月
  • 高濃度PFOAはマウスのみならずヒトのPPARαを活性化する, 玉田 葉月, 中川 智彦, ラムダン・ドニヒクマット, 伊藤 由起, 柳場 由絵, 上島 通浩, 那須 民江, 日本衛生学雑誌, 64, (2) 360 - 360,   2009年03月
  • ヒトPPARαを介したプラスチック可塑剤の脂質代謝への影響評価, 中村十識, 伊藤由起, 柳場由絵, 中川智彦, 森谷隆, 内藤久雄, 上島通浩, 那須民江, 日本衛生学雑誌, 62,   2007年03月01日

受賞

  •   2018年03月, 2017年度 日本衛生学会奨励賞
  •   2015年, 2014年度日本衛生学会最優秀論文賞
  •   2014年, 第84回日本衛生学会学術総会若手優秀演題賞
  •   2013年, 第83回日本衛生学会学術総会若手優秀演題賞
  •   2009年, 第79回日本衛生学会若手研究者のための学術総会会長賞(学会長賞)
  •   2008年, 第78回日本衛生学会学会長賞(若手対象)


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