Formation and persistence of DNA adducts from the carcinogen N-hydroxy-2-acetylaminofluorene in rat mammary gland in vivo.
The rat mammary carcinogen, N-hydroxy-2-acetylaminofluorene (N-hydroxy-2-AAF), has been proposed to be metabolically activated by mammary cytosolic N,O-acetyltransferase to a DNA binding species. To test this hypothesis, adult female Sprague-Dawley derived CD rats were treated, i.p., with 4.0 mg/kg [ring-3H]N-hydroxy-2-AAF. After 4 h, 1, 3, 14, and 28 days, the animals were killed, the mammary epithelium DNA was isolated and the carcinogen-deoxyribonucleoside adducts present were analyzed by high pressure liquid chromatography. At each time, only one adduct was detected and it was chromatographically identical to N-(deoxyguanosin-8-yl)-2-aminofluorene. The level of the adduct was maximal at 4 h (1.5 adducts/10(6) nucleotides) and then decreased, following first order kinetics with a t1/2 of 14.2 days. The detection of a single non-acetylated aminofluorene adduct is consistent with N,O-acyltransferase being involved in the metabolic activation of N-hydroxy-2-AAF in the rat mammary gland.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism*; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D014316:Tritium; D006881:Hydroxyacetylaminofluorene; D004247:DNA; D015073:2-Acetylaminofluorene; D000217:Acyltransferases; C029968:N-hydroxy-2-acetylaminofluorene N-O-acyltransferase