Toxicology and applied pharmacology

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

PMID 10222311


Human epidemiological studies suggest associations between acetylator phenotype and aromatic amine-induced tumors. The aromatic amine carcinogen 3,2'-dimethyl-4-aminobiphenyl (DMABP) induces colon, prostate, and urinary bladder tumors in the rat, and a rapid and slow acetylator rat model has been characterized. The formation of DNA adducts has been used as a valuable biomarker in tumorigenesis. In order to examine the relationship between the acetylation polymorphism and aromatic amine-induced cancer, DNA adducts were measured in three target organs (colon, prostate, and urinary bladder) and two nontarget organs (liver and heart) of male rapid (F344) and slow (WKY) acetylator inbred rats administered DMABP. Two DMABP-DNA adducts, N-(deoxyguanosin-8-yl)-DMABP (C8-DMABP) and 5-(deoxyguanosin-N2-yl)-DMABP (N2-DMABP), were identified in each target and nontarget organ examined. C8-DMABP-DNA 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 acetylator rats. These studies suggest that DMABP-induced DNA damage is acetylator phenotype-dependent in urinary bladder and prostate, two target organs for DMABP-induced tumorigenesis in the rat.