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

DNA ethenbases are promutagenic lesions formed by carcinogenssuch as vinyl chloride (VC). Their formation was investigatedin 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 weeksand in 7- and 14-week old, matched control animals. 1, N⁶Ethenoadenine(A) and 3, N⁴-ethenocytosine (eC) deoxyribonucleotides wereanalysed by immunoaffinity Purification and 32P-postlabelling.This postabelling method was compared with a radio-immunoassaymethod, which yielded similar results. Back-ground levels ofethenobases were found in DNA from the liver, lungs, kidneysand circulating lymphocytes of unexposed, control rats. In theliver, the following back-ground molar ratios of ethenobaseto parent base in DNA were detected (mean valuesx10–8):A/A, 0.04–0.05; C/C, 0.06–0.07. In the lungs, kidneysand circluating lympho-cytes, background levels of A and C rangedfrom 1.7 to 4.2x10–8 and from respectively. Followinga 5-day exposure to VC, a significant increase of A and D wasmeasured in hepatic DNA from rats sacrificed immediately aftertreatment. Further, a dose-dependent increase of both ethenoadducts was observed in liver DNA of VC-treated rats. Comparedto the 5-day exposure, 4-fold higher levels of A and C wereobserved in the liver of animals after 8 weeks of exposure.In contrast, there was an accumulation of C but not of A inlungs and kidneys. In circulating lymphocytes, no significantincrease of ethenobase levels above control values was observedafter 2 months of exposure to VC. Both etheno adducts were foundto be pesistent in liver DNA, after 2 months following the terminationof VC exposure. These results further support the notion thatDNA ethenogenesis. are critical lesions in VC-induced carcinogenesis.The possible contribution of lipid peroxidation products thatalso yield ethenobases, on the formation and persistence ofthese DNA adducts, remains to be clarified.