Tatsuta M, Iishi H, Baba M, Taniguchi H
Deparment of Gastrointestinal Oncology, Center for Adult Disease, Osaka, Japan.
Cancer Res. 1989 Aug 1;49(15):4199-203.
The effects of 6-hydroxydopamine (6-OHDA) on gastric carcinogenesis, on inhibition by tetragastrin of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and on the tissue catecholamine concentrations of the gastric wall and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received s.c. injections of tetragastrin (1 mg/kg of body weight every other day) in depot form, i.p. injections of 6-OHDA (42 mg/kg twice within 24 h and 105 mg/kg every 2 wk), or injections of both compounds after 25 wk of p.o. treatment with N-methyl-N'-nitro-N-nitrosoguanidine (100 micrograms/ml). At Wk 52, prolonged administration of tetragastrin or 6-OHDA had significantly reduced the incidence and the number of adenocarcinomas. Combined administration of tetragastrin and 6-OHDA significantly enhanced the inhibitory effects of tetragastrin or 6-OHDA on gastric carcinogenesis. Administration of 6-OHDA but not tetragastrin, caused a significant decrease in norepinephrine concentrations in the antral portion of the gastric wall. Rats treated with tetragastrin or 6-OHDA had a significantly lower labelling index of the antral mucosa, and this index was significantly decreased by combined administration of tetragastrin and 6-OHDA, as compared with labeling indices observed after treatment with tetragastrin or 6-OHDA alone. These findings indicate that 6-OHDA exerts a protective effect against gastric carcinogenesis and enhances the inhibitory effect of tetragastrin on gastric carcinogenesis. This effect of 6-OHDA may be related to its ability to inhibit cell proliferation of the antral mucosa.
在近交系Wistar大鼠中，研究了6-羟基多巴胺（6-OHDA）对胃癌发生的影响、对胃泌素抑制N-甲基-N'-硝基-N-亚硝基胍诱导的胃癌发生的影响，以及对胃壁组织儿茶酚胺浓度和胃黏膜标记指数的影响。大鼠皮下注射长效剂型的胃泌素（每隔一天1mg/kg体重），腹腔注射6-OHDA（24小时内两次，每次42mg/kg，每2周105mg/kg），或在口服N-甲基-N'-硝基-N-亚硝基胍（100μg/ml）25周后注射这两种化合物。在第52周时，长期给予胃泌素或6-OHDA可显著降低腺癌的发生率和数量。胃泌素和6-OHDA联合给药可显著增强胃泌素或6-OHDA对胃癌发生的抑制作用。给予6-OHDA而非胃泌素，可导致胃壁窦部去甲肾上腺素浓度显著降低。用胃泌素或6-OHDA处理的大鼠胃窦黏膜标记指数显著降低，与单独用胃泌素或6-OHDA处理后观察到的标记指数相比，胃泌素和6-OHDA联合给药可使该指数显著降低。这些发现表明，6-OHDA对胃癌发生具有保护作用，并增强胃泌素对胃癌发生的抑制作用。6-OHDA的这种作用可能与其抑制胃窦黏膜细胞增殖的能力有关。
