gastrins and trimethylenediamine

The effects of combined administration of bombesin (40 micrograms/kg body weight) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the development of large and small intestinal tumors and the incidence of their metastasis to the peritoneum induced by azoxymethane (AOM, 7.4 mg/kg body weight), the ODC activity of the intestinal wall, and the labeling index of the intestinal mucosa and tumor were investigated in inbred Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, s.c. injections of bombesin every other day, and drinking water containing DAP (2.5 g/l) until the end of the experiment at week 40. Administration of bombesin significantly increased the incidence of intestinal tumors at week 40. It had no influence on the location, size, histological features or depth of involvement of intestinal adenocarcinomas, but significantly increased the incidence of their metastasis to the peritoneum. It also resulted in a significant increase in the intestinal ODC activity and labeling index. Administration of DAP with bombesin significantly reduced the enhancement of intestinal carcinogenesis by bombesin. Although the combined use of DAP with bombesin had little or no influence on the location, size, histological features, or depth of involvement of intestinal cancers, the incidence of their metastasis was significantly reduced. DAP significantly attenuated bombesin enhancement of the intestinal ODC activity and labeling index. These findings indicate that ODC inhibition attenuated the enhancement of intestinal carcinogenesis and metastasis to the peritoneum.

Topics: Adenocarcinoma; Animals; Azoxymethane; Body Weight; Bombesin; Cell Division; Diamines; Drug Synergism; Gastrins; Intestinal Mucosa; Intestinal Neoplasms; Male; Neoplasm Metastasis; Ornithine Decarboxylase Inhibitors; Peritoneal Neoplasms; Rats; Rats, Wistar

The effects of combined administration of bombesin and the ornithine decarboxylase (ODC) inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the ODC activity of the gastric wall and the labelling index of the gastric mucosa were investigated in inbred Wistar rats. Rats were given drinking water containing MNNG (50 micrograms/ml) for 25 weeks and then drinking water containing DAP (2.5 g/l) and/or injections of 40 micrograms/kg body weight of bombesin in depot form every other day. Administration of bombesin alone resulted in significant increases in the incidence of gastric cancers, the ODC activity of the antral portion of the gastric wall and the labelling index of the antral mucosa. Administration of DAP with bombesin significantly reduced enhancement by the latter of gastric carcinogenesis, ODC activity of the antral portion of the gastric wall and the labelling index of the antral mucosa. Our results suggest that ODC inhibition attenuated the enhancement of gastric carcinogenesis by bombesin, and that this enhancement by bombesin was mediated by polyamine biosynthesis.

Topics: Adenocarcinoma; Animals; Bombesin; Diamines; Drug Interactions; Drug Synergism; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Male; Methylnitronitrosoguanidine; Ornithine Decarboxylase Inhibitors; Rats; Rats, Inbred Strains; Stomach; Stomach Neoplasms

The effects of combined administration of tetragastrin and the ornithine decarboxylase inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and the BUdR labelling indices of the fundic and antral mucosae, were investigated in inbred Wistar rats. Rats were given drinking water containing 2.5 g/l of DAP ad libitum and received alternate-day injections of 1 mg/kg body weight of tetragastrin in depot form after 25 weeks of oral treatment with MNNG. At week 52, prolonged administration of tetragastrin alone resulted in a significant reduction in the incidence and number of gastric cancers and a significant increase or decrease in the labelling indices of the fundic and antral mucosae, respectively. Concomitant administration of tetragastrin and DAP had no effect on the inhibition by tetragastrin of gastric carcinogenesis. With this treatment, the labelling index was significantly reduced in the fundic mucosa but not in the antral mucosa. These results suggest that ODC inhibitor does not attenuate tetragastrin inhibition of gastric carcinogenesis, and that anti-trophic action of tetragastrin on antral mucosa may be related to tetragastrin inhibition of gastric carcinogenesis.

Topics: Animals; Diamines; DNA; Eflornithine; Gastrins; Hydrogen-Ion Concentration; Male; Methylnitronitrosoguanidine; Ornithine Decarboxylase Inhibitors; Rats; Rats, Inbred Strains; Stomach Neoplasms; Tetragastrin