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

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 (epsilondA), N2, 3-epsilonG, 1, N2-etheno-2'-deoxyguanosine (1, N2-epsilondG), 3-(2'-deoxy-beta-d-erythro-pentofuranosyl) pyrimido[1,2-alpha]purin-10(3H) (M1dG), acrolein, crotonaldehyde and 4-HNE-derived dG adducts (assigned as AcrdG, CrdG, and 4-HNEdG respectively).;epsilondA 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 (13C 2)-VC for 1 week (6 h/day, 5 days/week). The results indicated that NA-epsilondA concentration did not show significant difference in the liver of adult and weanling rats after VC exposure. The distribution pattern of (13C2)-epsilondA 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-epsilondA, 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 17beta-estradiol (E2) supplemented OVX female rats, but not detected in OVX rats without E 2 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-epsilonG and 1, N6-epsilondA were observed in PCB153 or PCB126 exposed animals. Significant increases of 1, N6-epsilondA were observed in all animals exposed to TCDD and the ternary mixture. Increases of 1, N 2-epsilondG, 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.