Early Changes in the Gastric Mucosa with MNNG Exposure in the Rat

The morphology of the rat gastric mucosa was examined by light microscopy after short term-administration of a carcinogenic agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, at a dose of 50 mg/I in 0.04% of Tween 60), which was given to rats ad libitum from light-sealed bottles for 3 months. Tween 60 (0.04%) was given to rats as control for 3 months. Rats thus treated were sacrificed by decapitation at the end of 3 months after the beginning of the experiment. Tissue samples were taken from the area of the gastric mucosa designated before the experiment. Tissue sections three microns in thickness were stained with hematoxylin and eosin for histopathological evaluation and stained with azan for evaluation of proliferation of collagenous fiber. Slight atrophic changes, such as reduction in the number of parietal cells per unit area (78.8 ± 15.4 in the MNNG group and 110.1 ± 20.8 in the control group), shortened mucosal thickness (5.36 ± 0.69 in the MNNG group and 6.72 ± 0.53 in the control group), slight infiltration (grade 1) of inflammatory cell infiltration, and also slight proliferation (grade 1) of collagenous fibers were present in the fundic mucosa of rats treated with MNNG, while mucosal changes of hyperplastic gastritis, such as hyperplastic glands, increased mucosal thickness (2.77 ± 0.15 in the MNNG group; 2.64 ± 0.21 in the control group), and mild infiltration (grade 2) of inflammatory cells, and mild proliferation (grade 2) of collagenous fibers were present in the pyloric mucosa of rats treated with MNNG. Furthermore, in the pyloric mucosa, focal and diffuse lesions composed of atypical cells with erosions considered to be precancerous stage were present. Diffuse mucosal surface injuries (erosions) existed in both the fundic and pyloric mucosa. Development of gastric cancer does not seem to be involved in the background such as mucosa with atrophic gastritis but with hyperplastic gastritis in short term administration of MNNG.