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

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Abstract
The cell kinetics of pepsinogen isozyme I 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 μg/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 (100mg/kg b.w.) 1 h prior to death or continuously by osmotic minipump (120 μg/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<0.05) than in normal pyloric columns. After continuous BrdU administration, the life span of cells comprising PAPG was estimated to be ∼ 6–8 days while that of normal pyloric gland cells was ∼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.

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