HUMAN SENSITIVITY TO GENOTOXIC EFFECTS OF BUTADIENE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。“人类对丁二烯基因毒性影响的敏感性”研究正在检查职业性接触1,3-丁二烯的影响，这种化学物质用于制造合成橡胶和其他聚合物。它是一种已知的小鼠和大鼠致癌物，被列为可能的人类致癌物。在一项分子流行病学研究中，我们正在使用一种叫做生物标记的测量方法来评估最近职业暴露的影响。这是通过测量橡胶和石化工厂工人淋巴细胞中报告基因（hprt）突变的频率来完成的。还对接触丁二烯进行了其他测量。这些突变可能是暴露于丁二烯所致。暴露于约1ppm的丁二烯（目前允许的暴露限值）的工人发现突变频率增加，尿液中丁二烯代谢物的含量增加。观察到的特定突变的种类和频率的特征表明，暴露工人的细胞中缺失突变的增加。我们的观察提供了一个早期预警，即目前的职业暴露水平对丁二烯构成潜在的健康风险。这些结果可以用来确定进一步保护工人免受白血病风险的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The study of "Human sensitivity to the genotoxic effects of butadiene" is examining the effects of occupational exposure to 1,3-butadiene, a chemical used to make synthetic rubber and other polymers. It is a known carcinogen in mice and rats and is classified as a probable human carcinogen. We are using measurements called biological markers in a molecular epidemiology study to evaluate the effects of recent occupational exposures. This is done by measuring the frequency of mutations in a reporter gene (hprt) in lymphocytes from workers in rubber and petrochemical plants. Other measures of exposure to butadiene are also made. These mutations may be effects of exposure to butadiene. Workers exposed to about 1ppm of of butadiene (the current allowable exposure limit) were found to have an increased frequency of mutations and increased amounts of a metabolite of butadiene in their urine. Characterization of the kinds and frequencies of specific mutations observed indicated an elevation in deletion mutations in cells from exposed workers. Our obsservations provide an early warning that current levels of occupational exposure to butadiene pose a potential health risk. These results can be used to identify ways in which workers may be further protected from the risk of leukemia.