Effect of salt on cell proliferation and N-methyl-N'-nitro-N-nitrosoguanidine penetration to proliferative cells in the forestomach of rats.

We have studied the effect of intragastric instillation of 4.5 M NaCl on cell proliferation and carcinogen penetration into the forestomach of Wistar rats at different time intervals after salt exposure. Cells in the S-phase were labelled by incorporation of bromodeoxyuridine and located after immunohistochemistry. N-[3H]Methyl-N'-nitro-N-nitrosoguanidine ([3H]MNNG) was used as the carcinogen and penetration of [3H]MNNG to proliferative cells was determined by autoradiography. The number of cells in S-phase per millimetre epithelium length 12 h and 24 h after salt exposure (32.2 +/- 11.9 and 20.6 +/- 7.4) was significantly higher than in the control animals (9.4 +/- 3.6). No increase in cell proliferation occurred during the first 2 h after salt exposure. Microscopy also revealed oedema in the lamina propia. The forestomach blood flow was not influenced by the application of hypertonic saline. [3H]MNNG at a concentration of 40 micrograms/ml did not penetrate to the proliferative cells in the forestomach and no effect of salt pretreatment on carcinogen penetration was seen. The low penetration of [3H]MNNG to proliferative cells in the forestomach epithelium may explain why this concentration of MNNG given in drinking water over several weeks usually does not induce squamous cell carcinomas in the forestomach. The previously observed cocarcinogenic effect of salt on squamous cell cercinogenesis in the upper gastrointestinal tract could be due to the observed increase in cell proliferation after salt exposure.