Hallberg L M, Bechtold W E, Grady J, Legator M S, Au W W
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555-1110, USA.
Mutat Res. 1997 May 1;383(3):213-21. doi: 10.1016/s0921-8777(97)00004-9.
Exposure to high concentrations of butadiene has been shown to cause cancer among exposed workers. We have conducted a biomarker study to elucidate whether current butadiene exposure conditions are hazardous to workers. Twenty-four workers exposed consistently to butadiene were matched 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 exposed and control groups. In the challenge assay, the exposed group shows a consistent, but non-significant, increase in chromosome aberrations indicating some abnormality in DNA repair response. The observed dicentric frequency in the challenge assay (indicative of abnormal repair 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 abnormal repair response compared with non-smokers for both the control and exposed groups. A small subset of the studied workers were evaluated for toxicant-induced DNA repair deficiency using an independent cat-host cell reactivation (CAT-HCR) assay. When cigarette smokers and non-smokers were combined in our analysis, we observed that the exposed group (n = 9) had a significant reduction of DNA repair activities (p = 0.009) compared with the control group (n = 6). Cigarette smoking contributed significantly to the effect as exposed smokers (n = 4) had a significant reduction in DNA repair activities (p = 0.04) compared with exposed non-smokers. The results from the two independently conducted assays support each other and confirm the previously reported abnormal DNA repair response in another group of butadiene workers. In conclusion, our data indicates that exposure to environmental toxicants, such as butadiene, can cause DNA repair defects. Therefore, the current butadiene exposure conditions are still hazardous to workers. However, our data indicates that butadiene is not a potent genotoxic agent. Furthermore, the butadiene-induced effect is significantly enhanced by the cigarette smoking habit.
已表明，接触高浓度丁二烯会使接触该物质的工人患癌症。我们开展了一项生物标志物研究，以阐明当前丁二烯接触情况是否对工人有害。24名持续接触丁二烯的工人与19名接触丁二烯少得多的同事进行了匹配，这些同事作为我们的对照组。在标准细胞遗传学检测中，接触组和对照组的染色体畸变频率没有差异。在激发试验中，接触组的染色体畸变出现持续但不显著的增加，表明DNA修复反应存在某些异常。激发试验中观察到的双着丝粒频率（指示受损染色体的异常修复）与尿液中的丁二烯代谢物1,2 - 二羟基 - 4 -（N - 乙酰半胱氨酰）丁烷显著相关（r = 0.52；p = 0.04）。此外，无论是对照组还是接触组，吸烟者与非吸烟者相比，其修复反应始终异常。使用独立的猫宿主细胞再激活（CAT - HCR）检测法对一小部分研究对象工人进行了毒物诱导的DNA修复缺陷评估。当我们在分析中将吸烟者和非吸烟者合并时，我们观察到，与对照组（n = 6）相比，接触组（n = 9）的DNA修复活性显著降低（p = 0.009）。吸烟对这种影响有显著作用，因为接触丁二烯的吸烟者（n = 4）与接触丁二烯的非吸烟者相比，其DNA修复活性显著降低（p = 0.04）。两项独立进行的检测结果相互支持，并证实了先前在另一组丁二烯工人中报道的异常DNA修复反应。总之，我们的数据表明，接触环境毒物，如丁二烯，可导致DNA修复缺陷。因此，当前丁二烯接触情况对工人仍然有害。然而，我们的数据表明丁二烯不是一种强效的基因毒性剂。此外，吸烟习惯会显著增强丁二烯诱导的效应。
