PHENOBARBITAL AND 3-METHYLCHOLANTHRENE TREATMENT ALTERS PHASE-I AND PHASE-II ENZYMES AND THE SENSITIVITY OF THE RAT COLON TO THE CARCINOGENIC ACTIVITY OF AZOXYMETHANE

It has been hypothesized that cancer risk may be influenced by phase I and II drug-metabolizing enzyme systems. This study attempted to dete rmine the relationship between colon phase I and II enzyme activity an d the subsequent induction of aberrant crypt foci (ACF), preneoplastic lesions by azoxymethane (AOM), a colon-specific carcinogen. Phenobarb ital (PB) and 3-methylcholanthrene (MC) treatment (prototype hepatic i nducers of phase I and II enzymes) provided the framework to study the induction of phase I and II enzymes in the rat colonic mucosa. Follow ing induction for five consecutive days, the animals were given a sing le injection of AOM. Phase I and II enzymes were determined fluorometr ically and spectrophotometrically and ACF were identified microscopica lly. Phase I and II xenobiotic metabolizing enzymes were induced in th e rat colonic mucosa by prototype hepatic inducers. A lower number of ACF and crypt multiplicity was observed in animals induced with MC tha n in those in the non-induced and PB groups. Altered levels of phase I and II enzymes in the colon during preinitiation stages were associat ed with modulation in the growth of ACF, putative preneoplastic lesion s. (C) 1997 Elsevier Science Ltd.