WORKER GENETIC SUSCEPTIBILITY TO MUTAGENIC RISK

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Special populations at risk for workplace-related health effects include workers with genetic susceptibility to the mutagenic effects of occupational exposures due to inherited variants of metabolizing enzymes. We have previously demonstrated that workers exposed to vinyl chloride (VC) experience an increased frequency of biomarkers of mutagenic damage (mutant ras-p21 and/or mutant p53) in a dose-dependent fashion. At any given dose, however, workers can experience none, one or both of these biomarkers of mutagenic damage, suggesting that there may be inherited differences in VC-metabolizing enzymes that could account for these differences in effect from presumed similar exposures. In fact, genetic polymorphisms in VC-metabolizing enzymes have recently been related to an increased sister chromatid exchange frequency, a non-specific indicator of DNA damage, in VC-exposed workers. The purpose of the current study is to see if genetic polymorphisms in VC-metabolizing enzymes are also related to the more specific biomarkers of mutagenic damage (mutant ras-p21 and/or mutant p53) in VC-exposed workers. Restriction fragment length polymorphism techniques will be used to analyze DNA from sub-groups of VC-exposed workers with none, one or both biomarkers of mutagenic damage but with similar demographic and exposure characteristics for genetic polymorphisms in VC-metabolizing enzymes, and prevalences of the polymorphisms will be compared among the sub-groups. It is anticipated that workers with the polymorphisms will be more likely to have the biomarkers of mutagenic damage than similarly exposed workers without the polymorphisms and thus will be more likely to suffer form the subsequent carcinogenic and other health effects of VC exposure. If this proves to be correct, then such special populations at risk could be targeted for more stringent interventions to help prevent the occurrence of VC-related occupational diseases.