Enhancement of gastric carcinogenesis in dogs given N-methyl-N'-nitro-N-nitrosoguanidine following vagotomy.

Abstract

In an attempt to improve the method of induction of gastric cancer in dogs, selective vagotomy without drainage procedure was performed before administration of N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG). Twenty dogs were divided into two groups of 10 dogs (five beagles and five mongrels). The control group received MNNG alone. Dogs of the experimental group were vagotomized 2 months before administration of MNNG. MNNG solution (50 µg/ml) was administered in the drinking water for 12 months. In the vagotomized group, gastric adenocarcinomas were induced in all of eight effective cases, whereas in the control group they were seen in six of eight cases. Gastric cancer was found to be multiple in many dogs, but the majority of cancer lesions remained in the early stage. The total numbers of cancer lesions induced in the vagotomy and control group were 42 and 16, respectively. Vagotomy resulted in the production of more advanced cancers. One lesion in the control group and four lesions in the vagotomy group were advanced cancer invading the serosa. Advanced gastric cancers with metastases to the liver, lymph nodes, and lungs developed exclusively in two vagotomized dogs. Gastric acid secretion of the vagotomized dogs measured after termination of MNNG was reduced, on the average, to one-fourth of that of the control. The possible role of vagotomy in the enhancement of gastric carcinogenesis in dogs by MNNG is discussed in terms of the inactivation of MNNG in gastric juice and ulcerogenic action of the carcinogen to the gastric mucosa.