FORMATION AND ACCUMULATION OF DNA ETHENOBASES IN ADULT SPRAGUE-DAWLEYRATS EXPOSED TO VINYL-CHLORIDE

DNA ethenobases are promutagenic lesions formed by carcinogens such as vinyl chloride (VC), Their formation was investigated in 6-week old, male Sprague-Dawley rats exposed to 500 p.p.m. VC by inhalation (4 h/d ay, 5 days/week) for 1, 2, 4 or 8 weeks and in 7- and 14-week old, mat ched control animals, 1-N-6-Ethenoadenine (EA) and 3, N-4-ethenocytosi ne (epsilon C) deoxyribonucleotides were analysed by immunoaffinity pu rification and P-32-postlabelling. This postlabelling method was compa red with a radioimmunoassay method, which yielded similar results, Bac kground levels of ethenobases were found in DNA from the liver, lungs, kidneys and circulating lymphocytes of unexposed, control rats, In th e liver, the following background molar ratios of ethenobase to parent base in DNA were detected (mean values x 10(-8)): epsilon A/A, 0.04-0 .05; epsilon C/C, 0.06-0.07, In the lungs, kidneys and circulating lym phocytes, background levels of epsilon A and epsilon C ranged from 1.7 to 4.2 x 10(-8) and from 4.8 to 11.2 x 10(-8), respectively. Followin g a 5-day exposure to VC, a significant increase of epsilon A and EC w as measured in hepatic DNA from rats sacrificed immediately after trea tment, Further, a dose-dependent increase of both etheno adducts was o bserved in liver DNA of VC-treated rats, Compared to the 5-day exposur e, similar to 4-fold higher levels of epsilon A and epsilon C were obs erved in the liver of animals after 8 weeks of exposure, In contrast, there was an accumulation of epsilon C but not of epsilon A in lungs a nd kidneys, In circulating lymphocytes, no significant increase of eth enobase levels above control values was observed after 2 months of exp osure to VC, Both etheno adducts were found to be persistent in liver DNA, after 2 months following the termination of VC exposure, These re sults further support the notion that DNA etheno-bases are critical le sions in VC-induced carcinogenesis, The possible contribution of lipid peroxidation products that also yield ethenobases, on the formation a nd persistence of these DNA adducts, remains to be clarified.