Experimental gastric carcinogenesis in the rat: Effects of hypergastrinemia and acid secretion☆☆☆

Abstract The present experiments examined in rats the influence of chronic hypergastrinemia and the resulting gastric hyperacidity on induction of gastric adenocarcinoma by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Three groups of animals were studied: (A) control rats (no operation, normogastrinemia); (B) rats with antrectomy and Billroth II (normogastrinemia); and (C) rats with implantation of the antrum into the colon and Billroth II (hypergastrinemia). All rats were fed MNNG, 83 μg/ml, in drinking water for 6 months and were observed for 6 more months before being killed. The number, location, and histology of malignant gastric neoplasms were recorded. The incidence of tumors in the proximal gastric remnant of the Billroth II antrectomy rats was 88 percent, significantly greater than the incidence in the proximal gastric remnant (excluding the implanted antrum) of Billroth II antral implant rats (50 percent) or in control rats (50 percent). In addition, 19 gastric neoplasms were found in the 12 antra implanted into the transverse colon. Thus antrectomy Billroth II predisposed the animals to tumors, which was at least partially offset by hypergastrinemia. This suggests that gastric mucosa is more vulnerable to carcinogens after antrectomy and Billroth II, and the effects of hypergastrinemia (or acid secretion and mucosal growth) reduce this vulnerability. Hypergastrinemia did not protect the antrum from tumor induction when the antrum was removed from exposure to acid. These data suggest that in rats (1) antrectomy Billroth II predisposes to carcinogenically induced gastric cancer, (2) hypergastrinemia directly or indirectly decreases this predisposition, and (3) in the presence of hypergastrinemia and after removal from the acid stream, the antrum is highly vulnerable to the carcinogenic effects of MNNG.