Persistence of DNA adducts in rat liver and kidney after multiple doses of the carcinogen N-hydroxy-2-acetylaminofluorene.
Male and female Sprague-Dawley rats were treated by gastric intubation either 1, 2, 3, or 4 times at biweekly intervals with 10-mg/kg doses of the hepatocarcinogen of N-[ring-3H]-hydroxy-2-acetylaminofluorene. Then either 1 or 14 days following the last treatment, the concentrations of 2-aminofluorene and 2-acetylaminofluorene adducts in liver and kidney DNA were established. 2-Acetylaminofluorene adducts were found in male rat liver DNA only. The C-8-acetylated adduct, N-(deoxyguanosin-8-yl)-2-acetylaminofluorene, was detected only on the day following treatment at a concentration between 1.0 and 2.4 pmol/mg DNA. A second acetylated adduct, 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene, was found at both 1 and 14 days after treatment and, as a result, increased in concentration with repeated doses, from 0.2 pmol/mg DNA after one dose to 2.8 pmol/mg DNA after four treatments. The major adduct detected in male rat liver and the only adduct found in female rat liver and in kidney from either sex was N-(deoxyguanosin-8-yl)-2-aminofluorene. This adduct was slowly lost from the DNA and therefore increased in concentration with repetitive treatments as follows: male liver, 4.0 to 9.4 pmol/mg DNA; female liver, 11.4 to 30.6 pmol/mg DNA; male kidney, 1.1 to 1.8 pmol/mg DNA; and female kidney, 1.8 to 17.7 pmol/mg DNA. These data indicate that certain DNA adducts can accumulate in both target and non-target tissues and therefore suggest that persistence of DNA adducts per se is not sufficient for tumor induction.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000818:Animals; D004247:DNA / Q000378:metabolism*; D005260:Female; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism* / Q000633:toxicity; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013466:Sulfurtransferases / Q000032:analysis
D006881:Hydroxyacetylaminofluorene; D004247:DNA; D015073:2-Acetylaminofluorene; D013466:Sulfurtransferases