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 (epsilon A) in liver DNA. Mild-acid DNA hydrolysates were analyzed by high-performance liquid chromatography with photodiode array detection and fluorometry. The identification of OEG and epsilon A was confirmed by 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 rats showed adducts at 2 and 14 days of treatment with urethane in 5% ethanol, respectively. Neither OEG nor epsilon A was observed in control rats receiving water or 5% ethanol. Although these data are still preliminary, they appear to suggest that ethanol may inhibit formation of DNA adducts by urethane. Studies designed to produce more conclusive information about the role of ethanol in modifying DNA damage induced by urethane in vivo are in progress.
Sotomayor
R E
RE
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, MD 20708, USA.
Washington
M C
MC
D000241:Adenosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis*; D000431:Ethanol / Q000633:toxicity*; D006147:Guanine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014520:Urethane / Q000633:toxicity*; D014881:Water Supply
D018736:DNA Adducts; D009153:Mutagens; C007640:1,N(6)-ethenoadenosine; D014520:Urethane; D000431:Ethanol; D006147:Guanine; C032220:7-N-(2-oxoethyl)guanine; D004247:DNA; D000241:Adenosine