XRCC1, CYP2E1 and ALDH2 genetic polymorphisms and sister chromatid exchange frequency alterations amongst vinyl chloride monomer-exposed polyvinyl chloride workers

Ruey Hong Wong, Jung Der Wang, Ling Ling Hsieh, Tsun Jen Cheng

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Vinyl chloride monomer (VCM) is a known human carcinogen, which may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), and glutathione S-transferase T1 (GSTT1). A DNA-repair gene, X-ray repair cross-complementing group 1 (XRCC1, exon 10), may also be implicated in the process of VCM-related carcinogenesis. Thus, VCM-exposed workers with inherited susceptible metabolic and DNA-repair genotypes may experience an increased risk of genotoxiciy. This study was designed to investigate whether metabolic and DNA-repair genotypes affected sister chromatid exchange (SCE) frequency in occupationally VCM-exposed workers from polyvinyl chloride (PVC) manufacturing plants. Study subjects comprised 61 male workers having experienced VCM exposure, and 29 male controls. Questionnaires were administered to obtain detailed histories of cigarette-smoking habits, alcohol consumption behavior, and occupation. The frequency of SCE in peripheral lymphocytes was determined using a standardized method, and genotypes of CYP2E1, ALDH2, GSTT1 and XRCC1 were identified by the polymerase chain reaction (PCR) procedure. Our results demonstrated that smoking, age and VCM exposure and XRCC1 (P=0.03), CYP2E1 (P=0.04), and ALDH2 (P=0.08) were significantly associated with an increased SCE frequency. Further analysis of gene combinations, including CYP2E1, ALDH2 and XRCC1, revealed an increased trend for these genotypes to influence SCE frequencies for the low VCM-exposure group (P < 0.01), but not so for the high VCM-exposure group (P=0.29) or for controls (P=0.49). These results suggest that workers with susceptible metabolic and DNA-repair genotypes, may experience an increased risk of DNA damage elicited by VCM exposure.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
JournalArchives of Toxicology
Volume77
Issue number8
DOIs
Publication statusPublished - 2003 Aug 1

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

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