WORKER GENETIC SUSCEPTIBILITY TO MUTAGENIC RISK

有工作场所相关健康影响风险的特殊人群包括 具有遗传易感性的职业性工人的诱变效应 由于代谢酶的遗传变异而导致的暴露。我们之前已经 表明接触氯乙烯(VC)的工人会经历 突变损伤的生物标志物(突变型ras-p21和/或 突变型P53)以剂量依赖的方式。然而，在任何给定的剂量下，工作人员 可能不会经历任何、一个或两个生物标记物的突变损害， 提示维生素C代谢酶可能存在遗传差异 这可能解释了这些与假定的类似情况在效果上的差异 曝光。事实上，VC代谢酶的遗传多态已经 最近与姐妹染色单体交换频率增加有关，a 接触VC的工人的DNA损伤的非特异性指标。该计划的目的是 目前的研究是看看VC代谢酶的遗传多态是否 也与突变损伤(突变)的更特异的生物标志物有关 Ras-p21和/或突变型p53)。限制片段长度 多态技术将被用来分析来自亚群的DNA 接触VC的工人没有、有一个或两个都有突变损伤的生物标志物，但 具有相似的人口统计学和暴露特征的遗传多态 在VC代谢酶中，多态的流行程度将是 在亚组之间进行比较。据预计，拥有 多态将更有可能具有突变损伤的生物标记物 比没有多态的相似暴露的工人，因此将会更多 可能会遭受随后的致癌和其他健康影响 暴露于风险投资。如果这被证明是正确的，那么如此特殊的人口在 可以针对风险进行更严格的干预，以帮助防止 与VC有关的职业病的发生。

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.