Effects on sister chromatid exchange frequency of aldehyde dehydrogenase 2 genotype and smoking in vinyl chloride workers
Journal
Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Journal Volume
420
Journal Issue
1-3
Pages
99-107
Date Issued
1998
Author(s)
Abstract
Vinyl chloride monomer (VCM) is a human carcinogen. However, the exact mechanism of carcinogenesis remains unclear. VCM may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferases (GSTs). Thus workers with inherited variant metabolic enzyme activities may have an altered risk of genotoxicity. This study was designed to investigate which risk factors might affect sister chromatid exchange (SCE) frequency in polyvinyl chloride (PVC) workers. Study subjects were 44 male workers from three PVC factories. Questionnaires were administered to obtain detailed histories of cigarette smoking, alcohol consumption, occupations, and medications. SCE frequency in peripheral lymphocytes was determined using a standardized method, and CYP2E1, GSTM1, GSTT1 and ALDH2 genotypes were identified by the polymerase chain reaction (PCR). Analysis revealed that smoking status and exposure to VCM were significantly associated with increased SCE frequency. The presence of ALDH2 1-2/2-2 genotypes was also significantly associated with an elevation of SCE frequency (9.5 vs. 8.1, p<0.01). However, CYP2E1, GSTM1 or GSTT1 genotypes were not significantly associated with SCE frequency. When various genotypes were considered together, combination of CYP2E1 c1c2/c2c2 with ALDH2 1-2/2-2 showed an additive effect on SCE frequency. Similar results were also found for the combination of smoking with CYP2E1, or smoking with ALDH2. These results suggest that VCM workers with ALDH2 1-2/2-2 genotypes, who also smoke, may have increased risk of DNA damage. Copyright (C) 1998 Elsevier Science B.V.
SDGs
Other Subjects
aldehyde dehydrogenase; carcinogen; cigarette smoke; cytochrome p450; polyvinylchloride; vinyl chloride; adult; article; cancer risk; carcinogenesis; controlled study; enzyme activity; genotype; human; male; normal human; occupational cancer; occupational exposure; priority journal; sister chromatid exchange; smoking; Adult; Aldehyde Dehydrogenase; Carcinogens; Cytochrome P-450 Enzyme System; DNA Damage; DNA Primers; Drinking Behavior; Glutathione Transferase; Humans; Least-Squares Analysis; Male; Middle Aged; Occupational Exposure; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polyvinyl Chloride; Questionnaires; Risk Factors; Sister Chromatid Exchange; Smoking; Vinyl Chloride
Type
journal article
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