SISTER-CHROMATID EXCHANGES, GLUTATHIONE-S-TRANSFERASE THETA-DELETION AND CYTOGENETIC SENSITIVITY TO DIEPOXYBUTANE IN LYMPHOCYTES FROM BUTADIENE MONOMER PRODUCTION WORKERS

The magnitude of health risks to workers associated with current and p ast exposures to butadiene has been the subject of considerable recent debate. Butadiene is metabolized in-vivo and in-vitro to the genotoxi c intermediates 3,4-epoxybutene and diepoxybutane. Studies in animals and in in-vitro systems have clearly demonstrated that 1,3-butadiene i s a genotoxin and a potent inducer of sister-chromatid exchanges (SCEs ), Data on the genotoxicity of butadiene in humans is, however, limite d, Epidemiologic data indicate that butadiene is a probable human carc inogen. Recent work has further demonstrated that cultured lymphocytes from the approximately 20% of the Caucasian population that lack the glutathione S-transferase class theta gene (GSTT1) are relatively sens itive to the induction of cytogenetic damage by butadiene metabolites. Ln order to test whether butadiene exposure was associated with incre ases in SCE frequencies in peripheral blood lymphocytes and whether an y increase observed could be affected by the DEB sensitivity-GSTT1 del etion, we studied 40 workers employed in the production of butadiene. In these workers baseline frequencies of SCEs, diepoxybutane-induced S CE frequencies and GSTT1 deletion status were assessed. Questionnaires were administered to each worker and exposure to 1,3-butadiene was de termined using three separate approaches. Industrial hygiene personal sampling was used to measure breathing zone butadiene exposure and uri ne was collected to use in measurement of the urinary butadiene metabo lite 1,2-dihydroxy-4-(N-acetylcysteinyl-S-)-butane (M1), Exposure to b utadiene was generally below 2 ppm. The urinary metabolite M1 was foun d in all workers, but it did not correlate significantly with exposure . Six of 40 of the workers were GST theta-deleted DEB sensitive. No me asure of acute or chronic exposure to butadiene was associated with an increase in SCE frequency. However, smoking and DEB sensitivity-GSTT1 null status were each significantly associated with elevations in bas eline SCE frequency.