Higher DNA adduct levels in urinary bladder and prostate of slow acetylator inbred rats administered 3,2 '-dimethyl-4-aminobiphenyl

Human epidemiological studies suggest associations between acetylator pheno type and aromatic amine-induced tumors. The aromatic amine carcinogen 3,2'- dimethyl-4-aminobiphenyl (DMABP) induces colon, prostate, and urinary bladd er tumors in the rat, and a rapid and slow acetylator rat model has been ch aracterized. The formation of DNA adducts has been used as a valuable bioma rker in tumorigenesis. In order to examine the relationship between the ace tylation polymorphism and aromatic amine-induced cancer, DNA adducts were m easured in three target organs (colon, prostate, and urinary bladder) and t wo nontarget organs (liver and heart) of male rapid (F344) and slow (WKY) a cetylator inbred rats administered DMABP. Two DMABP-DNA adducts, N-(deoxygu anosin-8-y1)-DMABP (C8-DMABP) and 5-(deoxyguanosin-N-2-yl)-DMABP (N-2-DMABP ), were identified in each target and nontarget organ examined. C8-DMABP-DN A adduct levels were highest in liver and were dose related in liver, colon , urinary bladder, and prostate. DMABP-DNA adduct levels were significantly higher in the prostate and urinary bladder of slow acetylator vs rapid ace tylator rats. These studies suggest that DMABP-induced DNA damage is acetyl ator phenotype-dependent in urinary bladder and prostate, two target organs for DMABP-induced tumorigenesis in the rat. (C) 1999 Academic Press.