[Activation of proto-oncogenes induced by MNNG on primary culture of human gastric epithelium and immortalized human gastric epithelial cell line]

Abstract

Epidemiologic study has shown the association of nitrosamide compounds with the high incidence of stomach cancer in south China. To study the mechanism of gastric carcinogenesis, we have established an immortalized human gastric epithelial cell line GES-1. GES-1 cells and the normal gastric tissues were treated with different concentrations of MNNG for 24 hours. Point mutation at codon 12 of c-Ha-ras gene was found in cells and tissues (43%) as demonstrated by PCR-RFLP. Rearrangement of c-met gene and amplification of c-erbB2 gene were detected by Southern blot assay on the MNNG treated GES-1 cells. The results indicate that MNNG treatment was intimately associated with the activation of certain oncogenes. H-ras and c-met genes, serving as early targets of carcinogens may play important role in the carcinogenesis of human gastric epithelial cells.