Proliferation kinetics of pepsinogen altered pyloric gland cells in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

The cell kinetics of pepsinogen isozyme 1 altered pyloric gland (PAPG) cells with low pepsinogen isozyme 1 (Pg 1) content were analysed using double immunohistochemical staining for bromodeoxyuridine (BrdU) incorporation and Pg 1 in male WKY/NCrj rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After administration of 100 micrograms/ml MNNG for 10 weeks in the drinking water, carcinogenic insult was terminated and the animals killed two weeks later. BrdU was given either as a single i.p. injection (100 mg/kg b.w.) 1 h prior to death or continuously by osmotic minipump (120 micrograms/h) for 4, 7 and 10 days before killing. Immunogold-silver staining was used to detect BrdU and the avidin-biotin-peroxidase complex method adopted for demonstration of Pg 1. PAPG were found only in the MNNG treated group: their frequency was 4.1 +/- 0.6 per 100 pyloric glands. Almost no normal pyloric gland cells with high Pg 1 content demonstrated incorporation after BrdU flash labelling. However, a few pyloric gland cells in PAPG were labelled. The number of labelled cells in the pyloric columns containing PAPG was larger (P less than 0.05) than in normal pyloric columns. After continuous BrdU administration, the life span of cells comprising PAPG was estimated to be approximately 6-8 days while that of normal pyloric gland cells was approximately 11-13 days. Thus, the data indicate that PAPG cells demonstrate a degree of independence from surrounding pyloric glands with regard to proliferation kinetics, suggesting that PAPG is a preneoplastic lesion involved in gastric carcinogenesis.