ROS-induced DNA adducts in the rodents after exposure to superfund hazardous chemicals Public Deposited

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  • March 19, 2019
Creator
  • Gao, Lina
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
Abstract
  • The accumulation of oxidative DNA damage has been hypothesized as a key event in chemical carcinogenesis. In this study, oxidative DNA damage was evaluated in the livers of rats exposed to vinyl chloride (VC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3΄,4,4΄,5-pentachlorobiphenyl (PCB 126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,2΄,4,4΄,5,5΄-Hexachlorobiphenyl (PCB153). Eight oxidative DNA adducts were measured, 8-hydroxyl-2′-deoxyguanosine (8-OHdG), 1, N6-etheno-2’-deoxyadenosine (εdA), N2, 3-εG, 1, N2-etheno-2’-deoxyguanosine (1, N2-εdG), 3-(2′-deoxy-β-d-erythro-pentofuranosyl) pyrimido[1,2-α]purin-10(3H) (M1dG), acrolein, crotonaldehyde and 4-HNE -derived dG adducts (assigned as AcrdG, CrdG, and 4-HNEdG respectively). εdA is one of the promutagenic DNA adducts formed by VC, which can also be formed by lipid peroxidation. In this study, both adult and weanling Sprague-Dawley rats were exposed to 1100 ppm (13C2)-VC for 1 week (6 h/day, 5 days/week). The results indicated that NA-εdA concentration did not show significant difference in the liver of adult and weanling rats after VC exposure. The distribution pattern of (13C2)-εdA in liver, lung and kidney indicated that liver was the dominant target organ for VC toxicity in both adult and weanling rats. ROS-induced DNA adducts were detected in the liver of female intact, ovariectomized (OVX) and male Sprague-Dawley rats, including 8-OHdG, 1, N6-εdA, AcrdG, and CrdG. These animals were exposed to TCDD for 30 weeks after diethylnitrosamine (DEN) initiation. Induction of these adducts was consistently found in liver DNA of TCDD-treated intact female rats and 17β;-estradiol (E2) supplemented OVX female rats, but not detected in OVX rats without E2 supplement or male rats. These results further confirmed that the induction of these adducts occurs via a sex-specific and estrogen-dependent mechanism reported previously. Oxidative DNA damage was measured in liver DNA of female Sprague-Dawley rats following 53-week exposure of PHAHs, including PCB153, PCB126, TCDD, and the ternary mixture of TCDD, PCB126 and PeCDF. Increases of 8-OHdG, N2, 3-εG and 1, N6-εdA were observed in PCB153 or PCB126 exposed animals. Significant increases of 1, N6-εdA were observed in all animals exposed to TCDD and the ternary mixture. Increases of 1, N2-εdG, CrdG, AcrdG, 4-HNEdG and M1dG were detected in animals exposed to the ternary mixture, but not the TCDD treated rats compared to the control.
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  • In Copyright
Advisor
  • Swenberg, James A.
Degree
  • Doctor of Philosophy
Graduation year
  • 2011
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