PERSISTENCE OF DNA ADDUCTS IN RAT-LIVER AND KIDNEY AFTER MULTIPLE DOSES OF THE CARCINOGEN N-HYDROXY-2-ACETYLAMINOFLUORENE

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (4) , 1348-1354
Abstract
Male and female Sprague-Dawley rats were treated by gastric intubation 1, 2, 3 or 4 times at biweekly intervals with 10-mg/kg doses of the hepatocarcinogen N-[ring-3H]-hydroxy-2-acetylaminofluorene. One 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 1.0-2.4 pmol/mg DNA. A 2nd acetylated adduct, 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene, was found at both 1 and 14 days after treatment and increased in concentration from 0.2 pmol/mg DNA after 1 dose to 2.8 pmol/mg DNA after 4 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, 4.0-9.4 pmol/mg DNA; female liver, 11.4-30.6 pmol/mg DNA; male kidney, 1.1-1.8 pmol/mg DNA and female kidney, 1.8-17.7 pmol/mg DNA. Certain DNA adducts apparently can accumulate in both target and non-target tissues and so that persistence of DNA adducts per se is not sufficient for tumor induction.