Role of Persistent DNA-Bound Residues of 2-Acetylaminofluorene in Tumor Induction

摘要

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 (ring(sup 3)H)-N-hydroxy-2-acetylaminofluorene (AF) and acetylaminofluorene (AAF) adducts in liver and kidney DNA were established. AAF adducts were found in male rat liver DNA only. These data indicate that certain DNA adducts can accumulate in both target and nontarget tissues and, therefore, suggest that persistence of DNA adducts, per se, is not sufficient for tumor induction. In analogous experiments, male and female BALB/c mice were administered (ring(sup 3)H)-N-hydroxy-AAF. Only very low levels of liver DNA binding were detected (about 0.1 pmol/mg) DNA which is consistent with the much lower hepatocarcinogenicity of N-hydroxy-AAF for this species.