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 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 microg 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.
Department of Gastrointestinal Oncology, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Japan.
M
M
Tatsuta
H
H
Iishi
M
M
Baba
R
R
Hirasawa
K
K
Iseki
H
H
Yano
N
N
Sakai
H
H
Uehara
A
A
Nakaizumi
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens; D008297:Male; D008769:Methylnitronitrosoguanidine; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors*
D002273:Carcinogens; D009363:Neoplasm Proteins; D016211:Transforming Growth Factor alpha; D008769:Methylnitronitrosoguanidine