Changes in rat and human pepsinogen phenotypes induced by N′‐methyl‐N′nitro‐n‐nitrosoguanidine

Changes have been studied in human and rat pepsinogen phenotypes induced by N'-methyl-N'nitro-N-nitrosoguanidine (MMNG) in in vitro rat experiments and in vivo cultures of human and rat isolated gastric chief cells. In vivo the fastest migrating electrophoretic band decreased or disappeared as early as 3 weeks after the start of MNNG treatment. The changes, observed in 17 of 32 rats receiving MNNG, were permanent and consistently associated with pronounced histopathologic changes seen 10 months later (17 of 17). Comparable phenotypic changes were observed after 7 days only in MNNG-treated rat chief cell cultures. In human chief cell cultures a decrease of the Pg3 band, which is consistent with the "carcinogenic" phenotype, was observed in two of six preparations treated with MNNG. This early preceding change in phenotype preceding tumor formation may be useful as a diagnostic tool for the onset of gastric cancer.