High-resolution metabolomics of occupational exposure to trichloroethylene

作者：Douglas I. Walker, Karan Uppal, Luoping Zhang, Roel Vermeulen, Martyn T. Smith, Wei Hu, Mark P. Purdue, Xiaojiang Tang, Boris Reiss, Sungkyoon Kim, Laiyu Li, Hanlin Huang, Kurt D. Pennell, Dean P. Jones, Nathaniel Rothman, Qing Lan · 发表于：International Journal of Epidemiology · 年份：2016 · DOI：10.1093/ije/dyw218 · 被引用次数：111 · 研究领域：Carcinogens and Genotoxicity Assessment、Toxic Organic Pollutants Impact、Acute Lymphoblastic Leukemia research

Background: Occupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin’s lymphoma and kidney and liver cancer; however, TCE’s mode of action for development of these diseases in humans is not well understood. Methods: Non-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppma)] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population. Results: Metabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (β = 0.13, P-value = 3.6 × 10−5), glutamine (β = 0.08, P-value = 0.0013), cystine (β = 0.75, P-value = 0.0022), methylthioadenosine (β = −1.6, P-value = 0.0043), taurine (β = −2.4, P-value = 0.0011) and chenodeoxycholic acid (β = −1.3, P-value = 0.0...