Experimental gastric cancer.

Since Sugimura and Fujimura (1967) succeeded in selectively inducing gastric carcinomas in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (1), similar models for the induction of gastric carcinomas in other species by using MNNG and its ethyl derivative N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) have been established. The susceptibility to gastric carcinogenesis, the histologic types of gastric carcinomas induced, and their biological behavior depend on the mode of treatment, species, strain and/or sex. The organ specificity of MNNG correlates well with the level of DNA methylation in target and non-target tissues following oral administration in rats. The high concentration of methylated DNA bases in the stomach mucosa appears to result from thiol-mediated acceleration of the decomposition of MNNG. Experimental gastric carcinogenesis is markedly modified by various factors and agents, including bile reflux, bile acids, sodium chloride, and ulceration, indicating that both host and environmental factors contribute significantly to gastric carcinogenesis by chemical carcinogens.