Immunohistochemical demonstration of induction of pyloric glands with low pepsinogen 1 (Pg 1) content in rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine.
Three groups of male Fischer rats were given single doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 160 mg (group 1), 80 mg (group 2) and 40 mg (group 3)/kg body weight by gastric intubation. A fourth group was given drinking water containing 100 micrograms/ml of MNNG for 2 weeks, and a fifth group served as a control. Rats were killed in weeks 5, 8 and 12. Serial sections of the pyloric mucosa were examined by paradoxical concanavalin A (Con A) staining and pepsinogen isozyme 1 (Pg 1) immunostaining. All pyloric glands contained class III mucin as detected by paradoxical Con A staining. Most pyloric glands had a high Pg 1 content, but a few stained only weakly if at all. The percentage and number (No./500 normal-looking pyloric glands) of pyloric glands with a low Pg 1 content were 50.0 and 0.2 +/- 0.4 (week 5), 87.5 and 0.5 +/- 0.4 (week 8) and 100.0 and 1.2 +/- 1.0 (week 12) in group 1, 50.0 and 0.2 +/- 0.3 (week 8) and 87.5 and 0.5 +/- 0.4 (week 12) in group 2, and 30.0 and 0.2 +/- 0.4 (week 12) in group 4. No pyloric glands with a low Pg 1 content were found in groups 3 and 5. Thus the results showed significant dose-dependent induction (P less than 0.05-0.01) of altered pyloric glands demonstrating reduced Pg 1 content and their earlier appearance in groups given higher doses of MNNG. The results suggest that the appearance of pyloric glands with a low Pg 1 content may be a preneoplastic change in gastric carcinogenesis.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D006651:Histocytochemistry; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology; D008297:Male; D008769:Methylnitronitrosoguanidine; D009077:Mucins / Q000032:analysis; D010435:Pepsinogens / Q000032:analysis* / Q000276:immunology; D011230:Precancerous Conditions / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000201:enzymology*
D007527:Isoenzymes; D009077:Mucins; D010435:Pepsinogens; D008769:Methylnitronitrosoguanidine