ABNORMAL DNA-REPAIR ACTIVITIES IN LYMPHOCYTES OF WORKERS EXPOSED TO 1,3-BUTADIENE

Exposure to high concentrations of butadiene has been shown to cause c ancer among exposed workers, We have conducted a biomarker study to el ucidate whether current butadiene exposure conditions are hazardous to workers. Twenty-four workers exposed consistently to butadiene were m atched with 19 co-workers who had much less contact with butadiene and who served as our controls. In the standard cytogenetic assay, there was no difference in chromosome aberration frequencies between the exp osed and control groups. In the challenge assay, the exposed group sho ws a consistent, but non-significant, increase in chromosome aberratio ns indicating some abnormality in DNA repair response. The observed di centric frequency in the challenge assay (indicative of abnormal repai r of damaged chromosomes) is significantly correlated with a butadiene metabolite, 1,2-dihydroxy-4-(N-acetylcysteinyl)butane, in urine(r = 0 .52; p = 0.04). Furthermore, cigarette smokers had consistently abnorm al repair response compared with non-smokers for both the control and exposed groups, A small subset of the studied workers were evaluated f or toxicant-induced DNA repair deficiency using an independent cat hos t cell reactivation (CAT-HCR) assay. When cigarette smokers and non-sm okers were combined in our analysis, we observed that the exposed grou p (n = 9) had a significant reduction of DNA repair activities (p = 0. 009) compared with the control group (n = 6). Cigarette smoking contri buted significantly to the effect as exposed smokers (n = 4) had a sig nificant reduction in DNA repair activities (p = 0.04) compared with e xposed non-smokers. The results from the two independently conducted a ssays support each other and confirm the previously reported abnormal DNA repair response in another group of butadiene workers. In conclusi on, our data indicates that exposure to environmental toxicants, such as butadiene, can cause DNA repair defects. Therefore, the current but adiene exposure conditions are still hazardous to workers. However, ou r data indicates that butadiene is not a potent genotoxic agent. Furth ermore, the butadiene-induced effect is significantly enhanced by the cigarette smoking habit.