Colon cancer is induced by a single low dose of azoxymethane in fasted-refed rats

We reported previously that fasting-refeeding enhanced the growth of preneoplastic lesions in the colon of rats induced by 20 mg/kg of azoxymethane (AOM). Here we studied whether fasting-refeeding could also affect I) the induction of colon cancer by the same dose of AOM and 2) the induction of foci by lower doses of AOM that do not induce foci in fully fed rats. Fully fed and fasted-refed rats were given AOM by single subcutaneous injection, and the development of foci or tumors was evaluated three months or one year later. The results of the long-term carcinogenesis experiments showed that the total incidence of tumors was increased in the fasted-refed rats. Moreover, although fully fed rats developed foci only when injected with 7.5, 10, or 20 mg/kg of the carcinogen, a significant number of foci were also induced by 5 mg/kg in fasted-refed rats. The crypt multiplicity of foci was also higher when rats were exposed to fasting-refeeding, even when the number of foci was unchanged. These data suggest that growth perturbations induced by fasting-refeeding lead to the development of preneoplastic lesions with doses of AOM too low to trigger foci in fully fed rats and produce enhanced sensitivity to the development of intestinal tumors.