MUTATION OF HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE--LOCUS IN LYMPH

这项名为“人类对丁二烯基因毒性效应的敏感性”的研究正在研究职业接触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。工人接触丁二烯与造血系统癌症有关，特别是白血病。它还会导致几种生物体的基因突变。近年来，职业性接触已大大减少，因此很难用传统的流行病学方法评估与当前接触有关的风险。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。暴露于约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数量增加。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。在接触丁二烯的工人中发现的突变类型与在接触丁二烯及其代谢物的小鼠和培养细胞中发现的突变类似。突变频率与丁二烯接触的关系以及丁二烯接触的类型与已知与丁二烯有关的类型的关系表明，目前的暴露水平可能导致了这些影响。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。

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.