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- Title
High-resolution metabolomics of occupational exposure to trichloroethylene.
- Authors
Walker, Douglas I.; Uppal, Karan; Luoping Zhang; Vermeulen, Roel; Smith, Martyn; Wei Hu; Purdue, Mark P.; Xiaojiang Tang; Reiss, Boris; Sungkyoon Kim; Laiyu Li; Hanlin Huang; Pennell, Kurt D.; Jones, Dean P.; Rothman, Nathaniel; Qing Lan; Zhang, Luoping; Hu, Wei; Tang, Xiaojiang; Kim, Sungkyoon
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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 = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations.<bold>Conclusions: </bold>High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology.
- Subjects
CHINA; METABOLOMICS; PHYSIOLOGICAL effects of trichloroethylene; INDUSTRIAL hygiene; LYMPHOMAS; RENAL cancer; LIVER cancer; HYDROCARBON metabolism; BIOCHEMISTRY; HYDROCARBONS; KIDNEY tumors; LIVER tumors; MASS spectrometry; METABOLISM; OCCUPATIONAL diseases; REGRESSION analysis; RESEARCH funding; OCCUPATIONAL hazards; ENVIRONMENTAL exposure; CROSS-sectional method; CASE-control method
- Publication
International Journal of Epidemiology, 2016, Vol 45, Issue 5, p1517
- ISSN
0300-5771
- Publication type
journal article
- DOI
10.1093/ije/dyw218