Fasting/refeeding enhances the crypt multiplicity in rat colon carcinogenesis induced by azoxymethane

Aberrant crypt foci (ACF) are putative preneoplastic lesions of colon cancer which are being utilized currently as a biological end point to evaluate the induction and modulation of colon carcinogenesis. In rodents, caloric restriction reduces carcinogen-induced colon cancer incidence. The present study was designed to investigate the effect of fasting followed by refeeding on the development of ACF. Male Fisher 344 rats were fasted for 4 days and they were given a single injection of azoxymethane (AOM) at the dose of 20 mg/kg body weight on the first day of refeeding, and killed 3 months later. Controls were fed ad libitum and received the same dose of AOM. The number and crypt multiplicity (number of crypts/focus) of ACF were measured on the medial colon. No effect of fasting/refeeding was observed in the total number of foci/medial colon. On the contrary, rats fasted for 4 days and refed developed foci with higher number of crypts than fed controls. Our results are of particular interest because the crypt multiplicity, rather than the number of foci, is a consistent predictor of tumor incidence. As a consequence these data suggest a possible role of fasting/refeeding in enhancing the colon tumor outcome.