MUTATION OF HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE--LOCUS IN LYMPH

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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.