Enhancement by propranolol of the inhibitory effect of tetragastrin on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
The effects of combined administration of propranolol and tetragastrin on gastric acid secretion and the incidence and histological types of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin, 1 but not 0.2 mg/kg body weight in depot form after treatment with N-methyl-N'-nitro-N-nitrosoguanidine significantly reduced the incidence of adenocarcinoma of the glandular stomach. The adenocarcinomas that did develop in rats treated with the higher dose of tetragastrin had high mucin-producing activity and showed little or no typical glandular structure. A combination of propranolol (2 mg/kg) and tetragastrin (1 mg/kg) did not influence the inhibitory effect of gastrin on gastric carcinogenesis. However, concomitant administration of propranolol (2 mg/kg) and tetragastrin (0.2 mg/kg) caused a significant increase in gastric acid secretion and a reduction in the incidence of gastric carcinomas. With this treatment, the incidence of adenocarcinoma was similar to that of treatment with tetragastrin (1 mg/kg). Histological examinations showed that like the cancers in control rats, the adenocarcinomas induced in these rats were all highly differentiated.
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D004357:Drug Synergism; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000494:pharmacology*; D006965:Hyperplasia; D008297:Male; D008769:Methylnitronitrosoguanidine; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013758:Tetragastrin / Q000494:pharmacology*
D005755:Gastrins; D013758:Tetragastrin; D008769:Methylnitronitrosoguanidine; D011433:Propranolol