Metabolic proficiency and benzo[a]pyrene DNA adduct formation in APC(Min) mouse adenomas and uninvolved mucosa

Tumour formation may involve interactions between genetic factors and envir onmental carcinogens. Adenoma formation in APC(Min)/+ mice is associated ho mozygous adenomatous polyposis coli (APC) gene mutation, but the effects on carcinogen susceptibility are unknown. This study tests the hypothesis tha t APC(Min)/+ adenoma formation is accompanied by changes in metabolic profi ciency and carcinogen susceptibility, Cytochrome P450 (CYP)1A1/1A2, glutath ione S-transferase (GST)alpha, mu and pi classes and DNA adduct formation w ere assayed in adenomas and uninvolved mucose from APC(Min)/+ mice, before and after benzo[alpha]pyrene (B[alpha]P) treatment. In untreated adenomas a nd mucosa, CYP1A1/1A2 and B[alpha]P-DNA adducts were undetected but GST alp ha, mu and pi class enzymes were constitutively expressed. In adenomas, B[a lpha]P only induced CYP1A1/1A2 to low level while GST alpha and pi class en zymes were unaffected. A GST mu band which was absent from mucosa, was indu ced in adenomas, In mucosa, B[alpha]P induced CYP1A1/1A2 and GST alpha and pi, to high levels. B[alpha]P-DNA adduct levels were 56 +/- 15/10(8) nucleo tides (median +/- SE) in adenomas versus 89 +/- 19/10(8) nucleotides in muc osa (P < 0.0001), APC(Min) adenomas show reduced bioactivation capacity and sustain less DNA damage from B[alpha]P exposure, than APC(Min) uninvolved mucosa. These properties could influence mutagenesis and subsequent neoplas tic transformation of adenomas.