In utero and in vitro effects of benzene and its metabolites on erythroid differentiation and the role of reactive oxygen species.
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.
Badham
Helen J
HJ
Department of Pharmacology and Toxicology. Queen's University, Kingston, Ontario, Canada K7L 3N6.
Winn
Louise M
LM
D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006131:Growth Inhibitors / Q000633:toxicity; D006873:Hydroquinones / Q000633:toxicity; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018811:Maternal Exposure; D053858:Metabolic Networks and Pathways; D051379:Mice; D023421:Models, Animal; D019800:Phenol / Q000633:toxicity; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D004785:Environmental Pollutants; D006131:Growth Inhibitors; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D019800:Phenol; D013482:Superoxide Dismutase; D001554:Benzene; C031927:hydroquinone