Slow-release pellets of sodium butyrate do not modify azoxymethane (AOM)-induced intestinal carcinogenesis in F344 rats

Butyrate exerts anti-tumour effects in vitro, but not consistently in vivo, We previously demonstrated that the administration of slow-release gastro- resistant pellets of sodium butyrate increases apoptosis in the colon mucos a of rats, an effect which may protect against carcinogenesis. Therefore, w e studied whether the administration of butyrate pellets could protect rats against experimental colon carcinogenesis. Four to 5 week old male F344 ra ts were fed a high-fat (HF) diet (230 g/kg corn oil w/w) and treated s,c, w ith two injections (one week apart) of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight or saline. Rats were then divided into two groups: on e group received sodium butyrate pellets mixed into the diet (1.5% w/w) for 33 weeks (150 mg butyrate/day) and the second group received the high-fat diet with no butyrate, Administration of sodium butyrate pellets in the die t did not significantly affect colon carcinogenesis: the number of intestin al tumours/rat was 1.6 +/- 0.2 in controls and 2.1 +/- 0.2 in butyrate-fed rats (means +/- SE; P = 0,22, by ANOVA), while the incidence of intestinal tumours was 79 (23/29) and 90% (27/30) in controls and in butyrate-fed rats , respectively (P = 0.29 by Fisher's exact test). The level of apoptosis in the tumours was not affected by butyrate, nor was the expression of p21(CI P) a cell cycle-related protein. In conclusion, the current study indicates that butyrate does not protect against AOM-induced colon carcinogenesis in rats.