Molecular, biochemical and morphological aspects of the dynamics of rat stomach mucous membrane changes in experimental carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

The dependence of gastrocarcinogenesis on biochemical and morphological disorders of the stomach mucous membrane, i.e. epimolecular alteration of chromatin structure, inhibition of pepsinogen synthesis, alteration of ontogenetic heritage of glandular epithelium was studied in 450 random-bred white rats with the aid of a model of gastrocarcinogenesis induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This agent weakened the DNA-protein linkage in the chromatin. The irreversibility of this phenomenon coincided with the crucial point of the MNNG gastrocarcinogenesis (precancer sign appearance). The consequences of MNNG-induced specific alteration of epithelial stem cells became inherited (stomach adenocarcinoma development). In parallel with gastrocarcinogenesis, concomitant deficiency of pepsinogen-pepsin in the mucous membrane also developed. The data suggest that deficiency of the enzyme was in some degree obliged to alteration of pepsinogen mRNA synthesis.