FORMATION OF ETHENO AND OXOETHYL ADDUCTS IN LIVER DNA FROM RATS EXPOSED SUBCHRONICALLY TO URETHANE IN DRINKING-WATER AND ETHANOL

Exposure of Fisher-344 male rats to 10 000 ppm of urethane in drinking water for up to 90 days or in 5% ethanol for up to 14 days caused the formation of 7-[2'-oxoethyl]guanine (OEG) and 1,N-6-ethenoadenine (ep silon A) in liver DNA. Mild-acid DNA hydrolysates were analyzed by hig h-performance liquid chromatography with photodiode array detection an d fluorometry. The identification of OEG and epsilon A was confirmed b y coelution with the authentic standards. Forty and 67% of rats showed OEG and epsilon A adducts at 2 and 90 days of treatment with urethane in drinking water, respectively. In comparison, only 0 and 10% of rat s showed adducts at 2 and 14 days of treatment with urethane in 5% eth anol, respectively, Neither OEG nor epsilon A was observed in control rats receiving water or 5% ethanol. Although these data are still prel iminary, they appear to suggest that ethanol may inhibit formation of DNA adducts by urethane. Studies designed to produce more conclusive i nformation about the role of ethanol in modifying DNA damage induced b y urethane in vivo are in progress.