Promotion of intestinal carcinogenesis by dietary methionine

The metabolism of the polyamines spermidine and spermine is known to be enh anced in rapidly proliferating cells. Methionine is a precursor of the amin opropyl moieties of these amines, Therefore, it was of interest to study th e effects of a methionine supplemented diet on polyamine metabolism and pre neoplastic changes occurring in the intestinal tract of rats treated with t he chemical carcinogen azoxymethane (AOM), Adult Wistar rats received 15 mg AOM/kg body wt (i.p.) once each week for 2 weeks. Thereafter, the rats wer e randomly divided into two groups and received controlled isoenergetic die ts containing the same amount of folate, choline and vitamin B-12 during 12 weeks: one group was kept on a standard diet; the other was fed the same d iet, except that 1% L-methionine was added at the expense of carbohydrates. After 12 weeks, the administration of the methionine-supplemented diet sti mulated the turnover rate of ileal epithelial cells, indicating enhanced cr ypt cell proliferation. Furthermore, in this group, a 2-fold increase in th e number of aberrant hyperproliferative crypts and the appearance of tumors was observed in the colon. These effects were accompanied by the increased formation of spermidine and spermine due to the enhancement of S-adenosylm ethionine decarboxylase activity and by the upregulation of Cdx-1, a homeob ox gene with oncogenic potentials. The experimental data do not support the view of a chemopreventive effect of dietary methionine supplementation on intestinal carcinogenesis in rats, even at an early phase of preneoplastic development, but rather suggest that methionine promotes intestinal carcino genesis.