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-acetylamino-fluorene(N-hydroxy-2-AAF), has been proposed to be metabolically activatedby mammary cytosolic N,O-acetyltransferase to a DNA bindingspecies. To test this hypothesis, adult female Sprague-Dawleyderived CD rats were treated, l.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, themammary epithelium DNA was isolated and the carcinogen-deoxyribonucleosideadducts present were analyzed by high pressure liquid chromatography.At each time, only one adduct was detected and it was chromatographicallyidentical to N-(deoxyguanosin-8-yl)-2-aminofluorene. The levelof the adduct was maximal at 4 h (1.5 adducts/10⁶ nucleotides)and then decreased, following first order kinetics with a t_1/2of 14.2 days. The detection of a single non-acetylated aminofluoreneadduct is consistent with N,O-acyltransferase being involvedin the metabolic activation of N-hydroxy-2-AAF in the rat mammarygland.