In utero exposure to benzene increases embryonic c-Myb and Pim-1 protein levels in CD-1 mice.
Benzene is a known human leukemogen, but its role as an in utero leukemogen remains controversial. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. We hypothesize that in utero exposure to benzene may cause leukemogenesis by affecting the embryonic c-Myb/Pim-1 signaling pathway and that this is mediated by oxidative stress. To investigate this hypothesis, pregnant CD-1 mice were treated with either 800 mg/kg of benzene or corn oil (i.p.) on days 10 and 11 of gestation and in some cases pretreated with 25 kU/kg of PEG-catalase. Phosphorylated and total embryonic c-Myb and Pim-1 protein levels were assessed using Western blotting and maternal and embryonic oxidative stress were assessed by measuring reduced to oxidized glutathione ratios. Our results show increased oxidative stress at 4 and 24 h after exposure, increased phosphorylated Pim-1 protein levels 4 h after benzene exposure, and increased Pim-1 levels at 24 and 48 h after benzene exposure. Embryonic c-Myb levels were elevated at 24 h after exposure. PEG-catalase pretreatment prevented benzene-mediated increases in embryonic c-Myb and Pim-1 protein levels, and benzene-induced oxidative stress. These results support a role for ROS in c-Myb and Pim-1 alterations after in utero benzene exposure.
Wan
Joanne
J
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Winn
Louise M
LM
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D002374:Catalase / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011092:Polyethylene Glycols / Q000494:pharmacology; D020598:Proto-Oncogene Proteins c-myb / Q000032:analysis*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000032:analysis* / Q000378:metabolism; D017382:Reactive Oxygen Species
D020598:Proto-Oncogene Proteins c-myb; D017382:Reactive Oxygen Species; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D002374:Catalase; C496636:Pim1 protein, mouse; D051573:Proto-Oncogene Proteins c-pim-1; D005978:Glutathione; D001554:Benzene