INHIBITION BY TRANSFORMING-GROWTH-FACTOR (34-43)-ALPHA, A TGF-ALPHA 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 in duced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labell ing and apoptotic indices and TGF-alpha immunoreactivity of gastric mu cosa and gastric cancers was examined in Wistar rats. The rats receive d intraperitoneal injections of 10 or 20 mu g kg(-1) body weight of TG F(34-43)-alpha every other day after oral treatment with MNNG for 25 w eeks. Long-term administration of TGF(34-43)-alpha at both doses signi ficantly reduced the incidence of gastric cancers at the end of the ex periment in week 52. However, TGF(34-43)-alpha had no significant effe ct on the number, histological type or depth of involvement of gastric cancers. Administration of TGF(34-43)-alpha also significantly decrea sed the bromodeoxyuridine labelling index and TGF-alpha immunoreactivi ty, and significantly increased the apoptotic index of antral mucosa a nd gastric cancers. These findings indicate that TGF(34-43)-alpha inhi bits gastric carcinogenesis, and that its effects are mediated through decreased cell proliferation and TGF-alpha immunoreactivity and incre ased apoptosis induction in the gastric cancers.