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.
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