Inhibition by transforming growth factor (34-43)-α, a TGF-α antagonist, of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats

The effect of prolonged administration of transforming growth factor (34-43)-alpha, an antagonist of TGF-alpha, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labelling and apoptotic indices and TGF-alpha immunoreactivity of gastric mucosa and gastric cancers was examined in Wistar rats. The rats received intraperitoneal injections of 10 or 20 mu g kg(-1) body weight of TGF(34-43)-alpha every other day after oral treatment with MNNG for 25 weeks. Long-term administration of TGF(34-43)-alpha at both doses significantly reduced the incidence of gastric cancers at the end of the experiment in week 52. However, TGF(34-43)-alpha had no significant effect on the number, histological type or depth of involvement of gastric cancers. Administration of TGF(34-43)-alpha also significantly decreased the bromodeoxyuridine labelling index and TGF-alpha immunoreactivity, and significantly increased the apoptotic index of antral mucosa and gastric cancers. These findings indicate that TGF(34-43)-alpha inhibits gastric carcinogenesis, and that its effects are mediated through decreased cell proliferation and TGF-alpha immunoreactivity and increased apoptosis induction in the gastric cancers.