Tatsuta M, Iishi H, Yamamura H, Baba M, Yamamoto R, Taniguchi H
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Cancer Res. 1988 Mar 15;48(6):1591-5.
The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in depot form after treatment with N-methyl-N'-nitro-N-nitrosoguanidine resulted in a significant increase in gastric acid secretion, a significant decrease in the labeling index of the antral mucosa, and a significant decrease in the incidence of adenocarcinomas of the glandular stomach. Administration of cimetidine at 20 mg, but not 10 mg, per kg body weight with tetragastrin significantly reduced the gastric acid secretion induced by tetragastrin alone but did not influence the labeling index of the antral mucosa or the inhibitory effect of tetragastrin on gastric carcinogenesis. These findings indicate that gastric acid secretion has no influence on the development of gastric adenocarcinomas and that the inhibitory effect of tetragastrin on gastric carcinogenesis may be related to its effect in decreasing proliferation of cells in the antral mucosa.
在近交系Wistar大鼠中，研究了西咪替丁和四肽胃泌素联合给药对胃酸分泌、胃黏膜标记指数以及N-甲基-N'-硝基-N-亚硝基胍诱导的胃腺癌发生率的影响。在用N-甲基-N'-硝基-N-亚硝基胍治疗后，长期给予长效四肽胃泌素导致胃酸分泌显著增加、胃窦黏膜标记指数显著降低以及腺胃腺癌发生率显著降低。每千克体重给予20mg而非10mg西咪替丁与四肽胃泌素联合给药时，可显著降低单独使用四肽胃泌素诱导的胃酸分泌，但不影响胃窦黏膜标记指数或四肽胃泌素对胃癌发生的抑制作用。这些发现表明，胃酸分泌对胃腺癌的发生没有影响，并且四肽胃泌素对胃癌发生的抑制作用可能与其降低胃窦黏膜细胞增殖的作用有关。
