HUMAN SENSITIVITY TO GENOTOXIC EFFECTS OF BUTADIENE

1，3-丁二醇是一种广泛用于合成 橡胶和其他聚合物。 它在实验室动物中具有致癌性， 它对人类致癌作用的证据已经大大增加了 最近更新了对工作人员的评估， 橡胶工业显示出 丁二烯暴露和白血病 更完整地理解 接触丁二烯水平的工人面临的健康风险 目前使用的设备是迫切需要的。 此外，一个大 公众每天暴露于低水平的 丁二烯来自汽车排放物、香烟烟雾和其他来源。 我们 早些时候的记录表明，工人暴露于约1 ppm的丁二烯， hprt基因突变频率的显著升高 在他们的淋巴细胞中。 本项目的目的是评估 使用丁二烯的职业接触现状 暴露、效应和易感性的生物标志物。 期间 在第一轮赠款中，我们证实了我们早先的发现， 作业工人hprt突变淋巴细胞频率 研究提出 该项目的更新将解决三个知识差距：1） 更好地界定丁二烯接触与 生物学效应，2）表征由 丁二烯，和3）活化和解毒酶的作用， 代谢和遗传毒性。 以前研究过的 在苯乙烯-丁二烯聚合物工厂和一个新的 将对聚丁二烯工厂的人口进行评估。 具体 该项目的目标是：1）更准确地定义关系 暴露与HPRT突变诱导之间的关系 空气中丁二烯的浓度和尿中 代谢产物，2）确定淋巴细胞中hprt突变谱 克隆，和3）表征代谢在个体中的作用 通过测定丁二烯致突变作用的敏感性 多态性变异激活和解毒酶E12 E1， 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.