Investigating the Effects of In Utero Benzene Exposure on Murine Fetal Placenta DNA Repair Gene Expression
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Authors
Bile, Christian
Date
Type
thesis
Language
eng
Keyword
Benzene , In utero , Gene expression , Placenta , Non-homologous end joining , Homologous recombination , Environmental pollutant , Leukemia , Hematapoiesis , Reactive oxygen species
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Abstract
Benzene is a ubiquitous pollutant found in the environment, in car emissions, cigarette smoke, and at elevated levels in the industrial manufacturing of plastics, resins and dyes. Exposure to benzene results in carcinogenic and hematotoxic effects. In humans, adult exposure to the environmental pollutant is positively correlated with the development of leukemia and benzene may be associated with childhood leukemia following in utero exposure. The evidnce suggests that benzene and its metabolites are more toxic to the developing fetus, since the fetus has decreased detoxification and DNA repair abilities. While numerous studies implicate benzene crossing the placenta, being metabolized and causing oxidative stress and DNA damage ultimately leading to childhood leukemia, the mechanism by which it does this is unclear. It is possible that fetal exposure to benzene results in increased DNA damage that may be left mis repaired or unrepaired, leading to genotoxicity. By using a molecular toxicological approach, employing a CD-1 mouse in utero model, we tested whether in utero benzene exposure alters gene expression of critical DNA repair genes in fetal placentas. By conducting qRT-PCR tests for mRNA expression of critical NHEJ (non-homologous end joining) and HR (homologous recombination) genes, we showed that in utero benzene affects the regulation of 5 DNA repair genes following in utero exposure using two-way ANOVA. Xrcc4 showed significant increased gene expression at 24h, Xrcc5 showed significant increased expression at 6h, Xrcc6 showed no changes at any time point, Rad51 showed significant increased expression at 24h and Brca2 showed significant decreased expression at 2h and 6h. Results summarized in this thesis add to the growing evidence of the effects of in utero benzene exposure on fetal and placental DNA repair genes.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.