ACCELERATED PAPER: Formation and accumulation of DNA ethenobases in adult Sprague-Dawley rats exposed to vinyl chloride

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Abstract
DNA ethenbases are promutagenic lesions formed by carcinogens such as vinyl chloride (VC). Their formation was investigated in 9-week old, male Sprague-Dawley rats exposed to 500 p.p.m. VC by inhalation (4 h/day, 5 days/ week) for 1, 2, 4 or 8 weeks and in 7- and 14-week old, matched control animals. 1, N 6 Ethenoadenine (A) and 3, N 4 -ethenocytosine (eC) deoxyribonucleotides were analysed by immunoaffinity Purification and 32P-postlabelling. This postabelling method was compared with a radio-immunoassay method, which yielded similar results. Back-ground levels of ethenobases were found in DNA from the liver, lungs, kidneys and circulating lymphocytes of unexposed, control rats. In the liver, the following back-ground molar ratios of ethenobase to parent base in DNA were detected (mean values×10–8): A/A, 0.04–0.05; C/C, 0.06–0.07. In the lungs, kidneys and circluating lympho-cytes, background levels of A and C ranged from 1.7 to 4.2×10–8 and from respectively. Following a 5-day exposure to VC, a significant increase of A and D was measured in hepatic DNA from rats sacrificed immediately after treatment. Further, a dose-dependent increase of both etheno adducts was observed in liver DNA of VC-treated rats. Compared to the 5-day exposure, 4-fold higher levels of A and C were observed in the liver of animals after 8 weeks of exposure. In contrast, there was an accumulation of C but not of A in lungs and kidneys. In circulating lymphocytes, no significant increase of ethenobase levels above control values was observed after 2 months of exposure to VC. Both etheno adducts were found to be pesistent in liver DNA, after 2 months following the termination of VC exposure. These results further support the notion that DNA ethenogenesis. are critical lesions in VC-induced carcinogenesis. The possible contribution of lipid peroxidation products that also yield ethenobases, on the formation and persistence of these DNA adducts, remains to be clarified.

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