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High-resolution metabolomics of occupational exposure to trichloroethylene.
- Source :
-
International Journal of Epidemiology . Oct2016, Vol. 45 Issue 5, p1517-1527. 11p. - Publication Year :
- 2016
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *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
Subjects
Details
- Language :
- English
- ISSN :
- 03005771
- Volume :
- 45
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- International Journal of Epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 119421344
- Full Text :
- https://doi.org/10.1093/ije/dyw218