Anti-CYP2E1-induced by trichloroethylene exposure might be involved in the hypersensitivity syndrome

• Project/Area Number: 16K15383
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hygiene and public health
• Research Institution: Chubu University
• Principal Investigator: NASU Tamie 中部大学, 生命健康科学部, 特任教授 (10020794)
• Co-Investigator(Kenkyū-buntansha): 山ノ下 理 中部大学, 生命健康科学部, 講師 (50424924)
• Research Collaborator: WANG hailan ; YUAN yuan ; KAMIJIMA michihiro ; ITO yuki ; NAITO hisao ; KAWAMOTO yoshiyuki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: トリクロロエチレン / Hypersensitivity / CYP2E1抗体 / 性差 / 喫煙 / 飲酒 / 皮膚病型 / 疫学研究 / IgG / ELISA / 自己抗体 / 免疫沈降 / CYP2E1 / HLA多型

Outline of Final Research Achievements

We recruited 67 blood samples of trichloroethylene (TCE)-induced hypersensitivity syndrome (HS) patients, those of sex- and age-matched TCE HS-tolerant control and TCE non-exposed control, respectively. Serum CYP2E1 antibody was measured in each group using ELISA method. In men, the value of TCE HS-tolerant control was higher than that of TCE non-exposed control, while no difference was observed between the antibody levels of the former and patient group. In women, although the value of TCE HS-tolerant control was higher than that of TCE non-exposed control, that of patient group was lower than the TCE HS-tolerant control group, and no difference was observed between patients and TCE non-exposed group. Smoking and drinking habits did not affect TCE-induced serum CYP2E1 antibody in both sexes.

Academic Significance and Societal Importance of the Research Achievements

TCEによるHSはHLA-B*の遺伝子多型によって頻度が変わる。HLA-B*13：01はTCE HSの感受性遺伝子であり、この多型が多い中国や東南アジアでの発生頻度が多い。しかし発生頻度が少ないとはいえ、わが国でも発症している。これは作業環境のTCEをもっと低める必要性があると同時にHS発症のメカニズムを明らかにすることの重要性を示す。この研究はHSがTCE曝露約28日後に発症することにヒントを得て、TCEによるHS発症のメカニズムが明らかにすることが目的である。学術的に意義あることであり、予防につながるので社会的意義が大きい。

Research Products

• [Int'l Joint Research] 中国広東省職業病防治院(中国)
• [Int'l Joint Research] 中国広東省職業病防治院(中国)
• [Journal Article] Exposure reconstruction of trichloroethylene among patients with occupational trichloroethylene hypersensitivity syndrome (2018)
  • Author(s): NAKAJIMA Tamie、WANG Hailan、ITO Yuki、NAITO Hisao、WANG Dong、ZHAO Na、LI Hongling、QIU Xinxiang、XIA Lihua、CHEN Jiabin、WU Qifeng、LI Laiyu、HUANG Hanlin、KAMIJIMA Michihiro
  • Journal Title: Industrial Health Volume: 56 Issue: 4 Pages: 300-307
  • DOI: 10.2486/indhealth.2017-0202
  • NAID: 130007420192
  • ISSN: 0019-8366, 1880-8026
  • Peer Reviewed / Open Access
• [Journal Article] Occupational exposure limits for ethylene glycol monobutyl ether, isoprene, isopropyl acetate and propyleneimine, and classifications on carcinogenicity, occupational sensitizer and reproductive toxicant (2017)
  • Author(s): Azuma Kenichi、Kamijima Michihiro、Karita Kanae、Katoh Takahiko、Kawai Toshio、Kawamoto Toshihiro、Kishi Reiko、Kumagai Shinji、Kusaka Yukinori、Matsumoto Akiko、Miyagawa Muneyuki、Miyauchi Hiroyuki、Morimoto Yasuo、Nagano Kasuke、Naito Hisao、Nakajima Tamie、Nomiyama Tetsuo、Okuda Hirokazu、Omae Kazuyuki、Yano Eiji
  • Journal Title: Journal of Occupational Health Volume: 59 Issue: 4 Pages: 364-366
  • DOI: 10.1539/joh.17-0148-OP
  • NAID: 130005865537
  • ISSN: 1341-9145, 1348-9585
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 有機溶剤中毒予防の新しい展開 (2017)
  • Author(s): 那須民江
  • Journal Title: Peripheral Nerve Volume: 28(2) Pages: 202-207
  • Open Access
• [Journal Article] トリクロロエチレン健康リスク評価作業部会、トリクロロエチレン健康リスク評価作業部会報告書 トリクロロエチレンに係る健康リスク評価について (2017)
  • Author(s): 青木康展、上田佳代、内山巌男、上島通浩、祖父江友孝、武林亨、中杉修身、那須民江、新田裕史、野見山哲生、山崎新
  • Journal Title: 大気環境学会誌（J.Jpn.Soc.Environ) Volume: 52
  • Peer Reviewed / Open Access
• [Journal Article] Occupational Exposure Limits of lead, dimethylamine, n-butyl-2,3-epoxypropyl ether, and 2-ethyl-1-hexanol and carcinogenicity and occupational sensitizer classification (2016)
  • Author(s): Azuma K, Endo G, Endo Y, Hara K, Harada K, Hori H, Horie S, Horiguchi H, Ichiba M, Ichihara G, Ikeda M, Ishitake T, Ito A, Iwasawa S, Kamijima M, Karita K, Kawai T, Kawamoto T, Koizumi A, Kumagai S, Kusaka Y, Miyagawa M, Morimoto Y, Nagano K, Nasu T.
  • Journal Title: Journal of Occupational Health Volume: 58 Issue: 4_Special_Issue Pages: 385-387
  • DOI: 10.1539/joh.16-0155-OP
  • NAID: 130005410431
  • ISSN: 1341-9145, 1348-9585
  • Peer Reviewed / Open Access
• [Presentation] トリクロロエチレン(TCE)によるCYP2E1抗体上昇とhypersensitivity syndromeとの関係 (2019)
  • Author(s): 那須民江、王海蘭、袁媛、内藤久雄、伊藤由起、八谷寛、上島通浩
  • Organizer: 第93回日本産業衛生学会総会
• [Presentation] トリクロロエチレンによる過敏症症候群（HS）に対する曝露濃度と感受性因子の交互作用 (2018)
  • Author(s): 那須民江、王海蘭、伊藤由起、内藤久雄、柳場由絵、八屋寛、上島通浩
  • Organizer: 第88回日本衛生学会学術総会
• [Presentation] 有機溶剤中毒の新しい展開 (2017)
  • Author(s): 那須民江
  • Organizer: 第28回日本末梢神経学会学術集会
• [Presentation] 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- (2016)
  • Author(s): 那須民江
  • Organizer: 第89回日本産業衛生学会
  • Place of Presentation: 福島県文化センター（福島県福島市）
• [Book] Recommendation of Occupational Exposure Limits (2015-2016) (2016)
  • Author(s): Takebayashi T, Endo Y, Ikeda M, Kawai T, Kishi R, Koizumi A, Nagano K, Nasu T, Sakurai H, Satoh H, Shimizu H, Tanaka M, Tkheuchi Y, Yano E,Endo G, Fukushima T, Hara K, Hori H, Ichihara G, Karita K, Katoh T.
  • Publisher: J Occup Health