methylnitronitrosoguanidine and trimethylenediamine

The effects of combined administration of a catecholamine precursor, tyrosine methyl ester (TME), and an ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the norepinephrine (NE) concentration and ODC activity of the gastric wall, and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received s.c. injections of TME, 512 mg/kg body weight, every other day and drinking water with or without 2.5 g/l of DAP after 25 weeks of oral administration of MNNG. At week 52, administration of TME resulted in significant increases in the incidence of gastric cancers, in the NE concentration and the ODC activity of the antral portion of the gastric wall, and in the labeling index of antral epithelial cells. Administration of both TME and DAP significantly reduced the enhancements by TME of gastric carcinogenesis, NE concentration and ODC activity of the antral wall, and the labeling index of the antral mucosa. Our results suggest that ODC inhibition lessens enhancement by TME of gastric carcinogenesis and that the enhancement by TME of gastric carcinogenesis is mediated in part by polyamine biosynthesis.

Topics: Animals; Diamines; Enzyme Inhibitors; Male; Methylnitronitrosoguanidine; Norepinephrine; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Rats; Rats, Wistar; Stomach Neoplasms; Tyrosine

The effects of combined administration of NaCl and the ornithine decarboxylase (ODC) inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the ODC activity of the gastric wall and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats were given drinking water with or without 2.5 g/l DAP and chow pellets with and without 10% NaCl ad libitum after 25 weeks of oral administration of MNNG. At week 52 feeding 10% NaCl resulted in significant increases in the incidence of gastric cancers, in the ODC activity of the antral portion of the gastric wall and in the labeling index of antral epithelial cells. Administration of both NaCl and DAP significantly reduced the enhancements by NaCl of gastric carcinogenesis, ODC activity of the antral wall and the labeling index of antral epithelial cells. These results suggest that inhibition of ODC attenuates NaCl enhancement of gastric carcinogenesis and that enhancement by NaCl of gastric carcinogenesis is mediated by polyamine biosynthesis.

Topics: Animals; Carcinogens; Cocarcinogenesis; Diamines; Drug Interactions; Enzyme Inhibitors; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Rats; Rats, Wistar; Sodium Chloride; Stomach; Stomach Neoplasms

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

Inductions of 200-fold increase in ornithine decarboxylase activity within 6 hours and 9-fold increase in DNA synthesis within 3 hours in rat stomach mucosa were observed after a single oral dose of saturated NaCl solution. NaCl caused dose-dependent induction of ornithine decarboxylase activity at doses of 0.25 to 1. 5g /kg body weight, and of DNA synthesis at doses of 0. 5g to 1. 5g /kg body weight. Administration of 1,3-diaminopropane one hour before NaCl inhibited the induction of ornithine decarboxylase activity in the stomach mucosa 3 and 6 hours after NaCl administration, but a single dose of 1,3-diaminopropane itself induced ornithine decarboxylase after 16 hours.

Topics: Animals; Autoradiography; Diamines; DNA; Dose-Response Relationship, Drug; Enzyme Induction; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Ornithine Decarboxylase; Rats; Rats, Inbred F344; Sodium Chloride