Acute hematotoxicity of oral benzo(a)pyrene: the role of the Ah locus.
Our results show a marked acute hematotoxicity of oral benzo(a)pyrene (BaP) in D2 mice as well as the extreme resistance of BDF1 individuals to bone marrow toxicity induced by oral BaP. Continued oral BaP produced severe bone marrow depression in D2 mice affecting all myelopoietic lineages, but produced only moderate bone marrow depression in BDF1 mice affecting erythropoiesis only. Pluripotent hematopoietic stem cells were almost completely destroyed in D2 individuals, but only reduced to approximately 40% in BDF1 individuals after 7 days of BaP. D2 mice were killed by 13 days of continued oral BaP, but BDF1 mice were still alive and in good condition even after 19 days of continued oral BaP. Analysis of the bone marrow and peripheral blood changes showed that severe toxic chemical bone marrow depression in D2 mice by continued oral BaP cannot serve as an experimental model system of acute aplastic anemia.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006098:Granulocytes / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008214:Lymphocytes / Q000473:pathology; D008533:Megakaryocytes / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000033:anatomy & histology; D013950:Thymus Gland / Q000033:anatomy & histology
D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases