MUTATION OF HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE--LOCUS IN LYMPH

“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。工人接触丁二烯与血液形成系统的癌症，特别是白血病有关。它还会导致几种生物的基因突变。近年来，职业接触已大大减少，因此难以用传统的流行病学方法评估与目前接触有关的风险。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。在暴露于丁二烯的工人中发现的突变类型与暴露于丁二烯及其代谢物的小鼠和培养细胞中发现的突变相似。突变频率与暴露于丁二烯之间的关系，以及暴露于已知与丁二烯有关的人群的丁二烯类型之间的关系表明，目前的暴露水平可能会造成这些影响。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。

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. Butadiene exposure in workers has been associated with cancers of the blood forming system, particularly leukemias. It also causes genetic mutations in several organisms. Occupational exposures have been greatly reduced in recent years making it difficult to evaluate the risks related to current exposures by traditional epidemiological methods. 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 1 ppm 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. The types of mutations found in butadiene-exposed workers are similar to mutations seen in mice and cultured cells exposed to butadiene and its metabolites. The relationship of the frequency of mutation to butadiene exposure and of the types of butadiene exposure to those known to be associated with butadiene suggests that current levels of exposure may be causing these effects. Our observations 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.