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 (¹³C ₂)-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 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-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, N ²-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.