HUMAN SENSITIVITY TO GENOTOXIC EFFECTS OF BUTADIENE

1，3-丁二烯是一种广泛使用的化学品，用于制造合成 橡胶和其他聚合物。它在实验动物中是致癌的， 有大量证据表明它对人体有致癌作用。 最近更新了对#年工人的持续评价，加强了这一点 橡胶工业显示出显著的关联 接触丁二烯和白血病。更全面地了解 年接触丁二烯水平工人面临的健康风险 今天使用的设施是迫切需要的。此外，一个大型的 每天有1%的普通公众接触到低水平的 丁二烯来自汽车尾气、香烟烟雾等来源。我们 早些时候有文件表明，接触约1ppm丁二烯的工人有 HPRT基因突变频率的显著提高 在他们的淋巴细胞里。这个项目的目的是评估 职业暴露于丁二烯的现状 暴露、影响和敏感性的生物标记物。在.期间 这笔赠款的第一个周期，我们证实了我们早先发现的增加 工人HPRT突变淋巴细胞频率的研究这项研究建议 因为该项目的续订将解决三个知识差距：1) 更好地定义丁二烯接触和 生物效应，2)表征由病毒引起的突变类型 丁二烯，以及3)激活和解毒酶在体内的作用。 丁二烯的代谢和遗传毒性。以前研究过的 丁苯共聚装置工人人数和一个新的 将对聚丁二烯装置中的种群进行评估。具体的 该项目的目标是1)更准确地定义关系 重复测量在暴露和HPRT突变诱发之间的关系 空气中丁二烯浓度和尿液中 代谢物，2)测定淋巴细胞HPRT突变谱 克隆，以及3)表征个体新陈代谢的作用 测定丁二烯致突变效应的敏感性 激活和解毒酶CYP 2E1和 GST T1和M1。

1,3-Butadiene is a widely used chemical in the manufacture of synthetic rubber and other polymers. It is carcinogenic in laboratory animals and evidence of its carcinogenic effects in man have been greatly strengthened by a recent update of the ongoing evaluation of workers in the rubber industry which showed a significant association between butadiene exposure and leukemia. a more complete understanding of the health risks faced by workers exposed to levels of butadiene in facilities in use today is urgently needed. Furthermore, a large percentage of the general public is exposed daily to low levels of butadiene from auto emissions, cigarette smoke and other sources. We earlier documented that workers exposed to about 1 ppm of butadiene had a significant elevation in the frequency of mutations at the hprt gene in their lymphocytes. The purpose of this project is to evaluate current conditions of occupational exposure to butadiene using biological markers of exposure, effect and susceptibility. During the first cycle of this grant we confirmed our earlier finding of increased hprt mutant lymphocyte frequencies in workers. The research proposed for the renewal of this project will address three knowledge gaps: 1) better defining the relationship between butadiene exposure and biological effects, 2) characterizing the types of mutations induced by butadiene, and 3) the role of activating and detoxifying enzymes in the metabolism and genetic toxicity of butadiene. A previously studied population of workers in a styrene-butadiene polymer plant and a new population in a polybutadiene plant will be evaluated. The specific aims of the project are 1) to more precisely define the relationship between exposure and hprt mutation induction using repeated measurements of air concentration of butadiene and the concentration of a urinary metabolite, 2) to determine the spectrum of hprt mutations in lymphocyte clones, and 3) to characterize the role of metabolism in individual susceptibility to the mutagenic effects of butadiene by determining polymorphic variations activating and detoxifying enzymes CYP 2E1 and GST T1 and M1.