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 past exposures to butadiene has been the subject of considerable recent debate. Butadiene is metabolized in-vivo and in-vitro to the genotoxic intermediates 3,4-epoxybutene and diepoxybutane. Studies in animals and in-vitro systems have clearly demonstrated that 1,3-butadiene is a genotoxin and a potent inducer of sister-chromatid exchanges (SCEs). Data on the genotoxicity of butadiene in humans is, however, limited. Epidemiologic data indicate that butadiene is a probable human carcinogen. 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 sensitive to the induction of cytogenetic damage by butadiene metabolites. In order to test whether butadiene exposure was associated with increases in SCE frequencies in peripheral blood lymphocytes and whether any increase observed could be affected by the DEB sensitivity-GSTT1 deletion, we studied 40 workers employed in the production of butadiene. In these workers baseline frequencies of SCEs, diepoxybutane-induced SCE frequencies and GSTT1 deletion status were assessed. Questionnaires were administered to each worker and exposure to 1,3-butadiene was determined using three separate approaches. Industrial hygiene personal sampling was used to measure breathing zone butadiene exposure and urine was collected to use in measurement of the urinary butadiene metabolite 1,2-dihydroxy-4-(N-acetylcysteinyl-S-)-butane (M1). Exposure to butadiene was generally below 2 ppm. The urinary metabolite M1 was found in all workers, but it did not correlate significantly with exposure. Six of 40 of the workers were GST theta-deleted DEB sensitive. No measure 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 baseline SCE frequency.
Occupational Health Program, Harvard University School of Public Health, Boston, MA 02115, USA.
K T
KT
Kelsey
J K
JK
Wiencke
J
J
Ward
W
W
Bechtold
J
J
Fajen
D000328:Adult; D002070:Butadienes / Q000378:metabolism / Q000633:toxicity*; D002617:Chemical Industry; D004852:Epoxy Compounds / Q000633:toxicity*; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D016273:Occupational Exposure; D012854:Sister Chromatid Exchange
D002070:Butadienes; D004852:Epoxy Compounds; D009153:Mutagens; C007366:diepoxybutane; D005982:Glutathione Transferase