HUMAN SENSITIVITY TO GENOTOXIC EFFECTS OF BUTADIENE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项名为“人类对丁二烯基因毒性效应的敏感度”的研究正在研究职业暴露于1，3-丁二烯的影响。1，3-丁二烯是一种用于制造合成橡胶和其他聚合物的化学物质。它是一种在小鼠和大鼠身上已知的致癌物质，并被归类为可能的人类致癌物质。我们在一项分子流行病学研究中使用被称为生物标记物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厂工人淋巴细胞中报告基因(HPRT)的突变频率来完成的。此外，还制定了丁二烯暴露的其他指标。这些突变可能是接触丁二烯的影响。接触约1ppm丁二烯(目前允许的接触限值)的工人被发现突变频率增加，尿中丁二烯代谢物的量增加。对观察到的特定突变的种类和频率的表征表明，接触工人细胞中的缺失突变有所增加。我们的观察提供了一个早期警告，即目前职业性接触丁二烯的水平构成了潜在的健康风险。这些结果可以用来确定可以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.