bioactivation of the tobacco carcinogens 4aminobiphenyl 4abp and 2amino9hpyrido23bindole ac in human bladder rt4 cells occupational and tobacco exposure to aromatic amines aas including 4aminobiphenyl 4abp and 2naphthylamine 2na are associated with bladder cancer bc risk several epidemiological studies have also reported a possible role for structurally related heterocyclic aromatic amines haas formed in tobacco smoke or cooked meats with bc risk we had screened for dna adducts of 4abp 2na and several prominent haas formed in tobacco smoke or grilled meats including 2amino1methyl6phenylimidazo45bpyridine phip 2amino38dimethylmidazo45fquinoxaline meiqx and 2amino9hpyrido23bindole ac in the bladder dna of bc patients using liquid chromatographymass spectrometry we detected dna adducts of 4abp but not adducts of the other carcinogens in this study we have examined the capacity of rt4 cells an epithelial human bladder cell line to bioactivate aas and haas to dna damaging agents which may contribute to bc 4abp and ac formed dna adducts but dna adducts of 2na phip and meiqx were not detected 4abp dna adducts were formed at tenfold higher levels than ac adducts pretreatment of rt4 cells with naphthoflavone 110 m a specific cytochrome p450 1 cyp1 inhibitor decreased ac adduct formation by 50 but did not affect the level of 4abp adducts however cell pretreatment with 8methoxypsoralen 011 m a potent inhibitor of cyp2a resulted in a 90 decrease of 4abp dna adducts levels these data signify that cyp2a and cyp1a isoforms expressed in the target urothelium bioactivate 4abp and ac respectively and may be a critical feature of aromatic amineinduced urinary bladder carcinogenesis the bioactivation of other tobacco and environmental aas by bladder cyps and their ensuing bladder dna damage warrants further study