Attenuation by genistein of sodium-chloride-enhanced gastric carcinogenesis induced by N-methyl-N '-nitro-N-nitrosoguanidine in Wistar rats

The effects of prolonged administration of genistein, a tyrosine-kinase inh ibitor, an sodium-chloride-enhanced induction of gastric carcinogenesis ind uced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptoti c indices and vessel counts in the gastric mucosa and gastric cancers, were investigated in Wistar rats, After 25 weeks of the carcinogen treatment, r ats were fed chow pellets containing 10% sodium chloride and were given s.c . injections of genistein at dosages of IS mg/kg or 30 mg/kg body weight ev ery other day. In week 52, the incidence of gastric cancers was significant ly greater in rats fed sodium chloride than in untreated control rats. Prol onged administration of genistein at a dosage of 30 mg/kg, bur not 15 mg/kg , body weight significantly reduced the incidence of gastric cancers, which was increased by oral treatment with sodium chloride, Genistein at the hig her dose significantly decreased the labeling index and vessel counts of th e antral mucosa and the gastric cancers which were increased by treatment w ith sodium chloride and significantly increased the apoptotic index of the antral mucosa and the cancers (which was lowered by the treatment with sodi um chloride), These findings suggest that genistein attenuates gastric carc inogenesis promoted by sodium chloride, by inducing increased apoptosis and lower cell proliferation and angiogenesis of antral mucosa and gastric: ca ncers. (C) 1999 Wiley-Liss, Inc.