Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice.
Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted.
Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen's University, Kingston, ON K7L3N6, Canada.
Nicola A
NA
Philbrook
Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen's University, Kingston, ON K7L3N6, Canada; School of Environmental Studies, Queen's University, Kingston, ON K7L3N6, Canada. Electronic address: winnl@queensu.ca.
Louise M
LM
Winn
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism; D004249:DNA Damage; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D011247:Pregnancy; D011401:Promoter Regions, Genetic
C493968:Cdkn2b protein, mouse; D050762:Cyclin-Dependent Kinase Inhibitor p15; D006657:Histones; D001554:Benzene
Benzene; DNA methylation; Fetal liver; Histone modifications; Maternal bone marrow; in utero