Effect of N-methyl-N'-nitro-N-nitrosoguanidine on gastroduodenal epithelial proliferation in Wistar/Lewis rats.

The effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on gastroduodenal epithelial proliferation p]rior to the development of frank neoplasia was studied in inbred LEW rats with or without gastric ulcers. The rats received either MNNG (100 gm/liter) in the drinking water or plain water. After 4 weeks, some rats in the MNNG-treated and control groups were given injections of tritiated thymidine and killed 1 hour later. In other rats, either an ulcer of the fundic mucosa was formed by a suction biopsy tube at laparotomy or a sham operation was performed. At 2 and 4 weeks after the operation, these rats were given injections of tritiated thymidine and killed 1 hour later. Sections of fundus, antrum, and duodenum were prepared for light autoradiography. MNNG treatment stimulated gastroduodenal epithelial proliferation, expanded the proliferative zone (PZ), and in the duodenum caused marked villus blunting and elongation of the crypts. No additional effect of the fundic ulcer or sham operation on gastroduodenal proliferation could be determined. The MNNG-induced expansion of the PZ occurred in a downward direction. Thus theories of carcinogenesis should include not only the expansion of the PZ toward the mucosal surface but also the possibility of expansion of the PZ toward the base of the mucosa.