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High-resolution metabolomics of occupational exposure to trichloroethylene
DC Field | Value | Language |
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dc.contributor.author | Walker, Douglas I. | - |
dc.contributor.author | Uppal, Karan | - |
dc.contributor.author | Zhang, Luoping | - |
dc.contributor.author | Vermeulen, Roel | - |
dc.contributor.author | Smith, Martyn | - |
dc.contributor.author | Hu, Wei | - |
dc.contributor.author | Purdue, Mark P. | - |
dc.contributor.author | Tang, Xiaojiang | - |
dc.contributor.author | Reiss, Boris | - |
dc.contributor.author | Kim, Sungkyoon | - |
dc.contributor.author | Li, Laiyu | - |
dc.contributor.author | Huang, Hanlin | - |
dc.contributor.author | Pennell, Kurt D. | - |
dc.contributor.author | Jones, Dean P. | - |
dc.contributor.author | Rothman, Nathaniel | - |
dc.contributor.author | Lan, Qing | - |
dc.date.accessioned | 2023-04-19T06:58:30Z | - |
dc.date.available | 2023-04-19T06:58:30Z | - |
dc.date.created | 2018-09-07 | - |
dc.date.issued | 2016-10 | - |
dc.identifier.citation | International Journal of Epidemiology, Vol.45 No.5, pp.1517-1527 | - |
dc.identifier.issn | 0300-5771 | - |
dc.identifier.uri | https://hdl.handle.net/10371/190686 | - |
dc.description.abstract | 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 (ppm(a))] 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 (beta = 0.13, P-value = 3.6 x 10(-5)), glutamine (beta = 0.08, P-value = 0.0013), cystine (beta = 0.75, P-value = 0.0022), methylthioadenosine (beta = -1.6, P-value = 0.0043), taurine (beta = -2.4, P-value = 0.0011) and chenodeoxycholic acid (beta = -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 end-points supported known disease associations. Conclusions: High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology. | - |
dc.language | 영어 | - |
dc.publisher | Oxford University Press | - |
dc.title | High-resolution metabolomics of occupational exposure to trichloroethylene | - |
dc.type | Article | - |
dc.identifier.doi | 10.1093/ije/dyw218 | - |
dc.citation.journaltitle | International Journal of Epidemiology | - |
dc.identifier.wosid | 000393184400025 | - |
dc.identifier.scopusid | 2-s2.0-85018246986 | - |
dc.citation.endpage | 1527 | - |
dc.citation.number | 5 | - |
dc.citation.startpage | 1517 | - |
dc.citation.volume | 45 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kim, Sungkyoon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ADENOSINE-DEAMINASE ACTIVITY | - |
dc.subject.keywordPlus | MASS-SPECTROMETRY | - |
dc.subject.keywordPlus | WIDE ASSOCIATION | - |
dc.subject.keywordPlus | FUNCTIONAL IMPLICATIONS | - |
dc.subject.keywordPlus | CHLORINATED SOLVENTS | - |
dc.subject.keywordPlus | TRICHLOROACETIC-ACID | - |
dc.subject.keywordPlus | KIDNEY-DISEASE | - |
dc.subject.keywordPlus | RISK-FACTORS | - |
dc.subject.keywordPlus | LARGE-SCALE | - |
dc.subject.keywordPlus | WORKERS | - |
dc.subject.keywordAuthor | Exposome | - |
dc.subject.keywordAuthor | Metabolic phenotype | - |
dc.subject.keywordAuthor | VOC exposure | - |
dc.subject.keywordAuthor | Bioeffect monitoring | - |
dc.subject.keywordAuthor | Population screening | - |
dc.subject.keywordAuthor | High-resolution metabolomics | - |
dc.subject.keywordAuthor | Trichlororoethylene | - |
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