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研究子宫内苯暴露对母源和胎源CD-1小鼠表观遗传修饰的影响。

Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice.

作者信息

Philbrook Nicola A, Winn Louise M

机构信息

Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen's University, Kingston, ON K7L3N6, Canada.

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.

出版信息

Toxicol Appl Pharmacol. 2015 Nov 15;289(1):12-9. doi: 10.1016/j.taap.2015.08.019. Epub 2015 Sep 1.

Abstract

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.

摘要

接触普遍存在的环境污染物苯与成人白血病呈正相关,并且宫内接触后可能与儿童白血病有关。虽然众多研究表明氧化应激和DNA损伤在苯介导的致癌作用中发挥作用,但新出现的证据表明表观遗传调控的改变可能也参与其中。本研究旨在确定CD-1小鼠宫内接触苯后DNA甲基化和/或各种组蛋白修饰是否发生改变。评估了肿瘤抑制基因p15的全基因组DNA甲基化和启动子特异性甲基化。此外,通过蛋白质印迹法评估了组蛋白H3、H4和H3K56的乙酰化水平,以及组蛋白H3K9和H3K27的甲基化水平。苯暴露后观察到母体骨髓全基因组DNA甲基化显著降低;然而,在胎儿肝脏中未检测到对全基因组DNA甲基化的影响。此外,在母体骨髓和胎儿肝脏中,未观察到苯暴露对p15启动子甲基化或任何检测到的组蛋白修饰有影响。这些结果表明,本研究中使用的方法未揭示宫内接触苯后DNA甲基化和组蛋白修饰的改变;然而,有必要在全基因组/表观基因组水平以及苯诱导致癌作用的后期阶段对这些修饰进行进一步实验研究。

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