Department of Pharmacology and Toxicology. Queen's University, Kingston, Ontario, Canada K7L 3N6.
Toxicol Appl Pharmacol. 2010 May 1;244(3):273-9. doi: 10.1016/j.taap.2010.01.002. Epub 2010 Jan 18.
Benzene is a ubiquitous occupational and environmental toxicant. Exposures to benzene both prenatally and during adulthood are associated with the development of disorders such as aplastic anemia and leukemia. Mechanisms of benzene toxicity are unknown; however, generation of reactive oxygen species (ROS) by benzene metabolites may play a role. Little is known regarding the effects of benzene metabolites on erythropoiesis. Therefore, to determine the effects of in utero exposure to benzene on the growth and differentiation of fetal erythroid progenitor cells (CFU-E), pregnant CD-1 mice were exposed to benzene and CFU-E numbers were assessed in fetal liver (hematopoietic) tissue. In addition, to determine the effect of benzene metabolite-induced ROS generation on erythropoiesis, HD3 chicken erythroblast cells were exposed to benzene, phenol, or hydroquinone followed by stimulation of erythrocyte differentiation. Our results show that in utero exposure to benzene caused significant alterations in female offspring CFU-E numbers. In addition, exposure to hydroquinone, but not benzene or phenol, significantly reduced the percentage of differentiated HD3 cells, which was associated with an increase in ROS. Pretreatment of HD3 cells with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) prevented hydroquinone-induced inhibition of erythropoiesis, supporting the hypothesis that ROS generation is involved in the development of benzene erythrotoxicity. In conclusion, this study provided evidence that ROS generated as a result of benzene metabolism may significantly alter erythroid differentiation, potentially leading to the development of Blood Disorders.
苯是一种普遍存在的职业和环境毒物。产前和成年期暴露于苯会导致再生障碍性贫血和白血病等疾病的发生。苯毒性的机制尚不清楚；然而，苯代谢物产生的活性氧（ROS）可能发挥作用。关于苯代谢物对红细胞生成的影响知之甚少。因此，为了确定宫内暴露于苯对胎儿红系祖细胞（CFU-E）生长和分化的影响，将 CD-1 怀孕小鼠暴露于苯中，并评估胎肝（造血）组织中的 CFU-E 数量。此外，为了确定苯代谢物诱导的 ROS 生成对红细胞生成的影响，将 HD3 鸡红细胞母细胞暴露于苯、苯酚或对苯二酚，然后刺激红细胞分化。我们的结果表明，宫内暴露于苯会导致雌性后代 CFU-E 数量发生显著变化。此外，暴露于对苯二酚而非苯或苯酚会显著降低分化的 HD3 细胞的百分比，这与 ROS 的增加有关。HD3 细胞用聚乙二醇-缀合超氧化物歧化酶（PEG-SOD）预处理可防止对苯二酚诱导的红细胞生成抑制，支持 ROS 生成参与苯致红细胞毒性发展的假说。总之，这项研究提供了证据表明，苯代谢产生的 ROS 可能会显著改变红细胞分化，从而可能导致血液疾病的发生。
