EVIDENCE OF ANTI-BENZO[A]PYRENE DIOLEPOXIDE-DNA ADDUCT FORMATION IN HUMAN COLON MUCOSA

As risk factors for colorectal cancer include consumption of foods pot entially contaminated with polycyclic aromatic hydrocarbons (PAHs), th e level of droxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-ant i-BPDE] bound to DNA of human colon mucosa samples was quantified by a sensitive and specific HPLC/fluorescence method (Alexandrov et al., C ancer Res, 51, 6248-6253, 1992), (+)-anti-BPDE-DNA adducts were detect ed in four out of seven colon mucosa samples but not in any of 11 huma n pancreas samples from smokers and non-smokers. Adduct levels in huma n colon varied between 0.2 and 1.0 (+)-anti-BPDE-DNA adducts/10(8) nuc leotides, Our results provide evidence that: (i) the DNA in human colo n cells can be damaged by benzo[a]pyrene, possibly derived from diet a nd/or tobacco smoke; (ii) DNA adduct formation in human colon epitheli um proceeds via the diol epoxide pathway; (iii) benzo[a]pyrene and oth er PAHs could play a role in the etiology of human colorectal cancer.