Changes in Pepsinogen Isozymes in Stomach Carcinogenesis Induced in Rats by N-Methyl-N’ -nitro-N-nitrosoguanidine 2

Abstract

Changes in the isozymes of pepsinogen (Pg) separated from the glandular stomachs of rats were studied by polyacrylamide gel electrophoresis during carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), from the beginning of MNNG administration to 3 months after the end of its 7-month regimen. In 13 of 25 rats killed successively, one (Pg 1) of the three pepsinogen isozymes (Pg 1, 3, 4) normally present in the pyloric mucosa had decreased or disappeared. It decreas was observed from 1 week after the beginning of MNNG treatment to at least 3 months after the end of the 7-month MNNG administration. Remarkable histopathologic changes were found from 8 months after MNNG was given, and rats showing such unusual histopathologic alterations also had changes in their pepsinogen isozyme pattern. In 4 of 27 rats, two (Pg 1, 2) of the four isozymes of pepsinogen (Pg 1-4) in the fundic mucosa decreased or disappeared from 3 months after the beginning of MNNG treatment to at least 2 months after the end of its 7-month administration. Histopathologic changes induced by MNNG were not as remarkable in the fundic mucosa as in the pyloric mucosa.

Expression of Cathepsin E and Its Suppression with Intestinalization in Epithelial Cells and Tumor Cells in Rat Glandular Stomach Treated with N-methyl-N'-nitro-N-nitrosoguanidine.

“…Thus the data suggest that a phenotypic shift from gastric to intestinal epithelial cell type occur with progression of gastric cancer in line with earlier findings 2,23 . Rather than intestinal metaplasia, pepsinogen altered pyloric glands in rats, which can be detected immunohistochemically, have recently been suggested to be preneoplastic lesions in rats [24][25][26][27] . Fig.…”

Dendritic Cell Appearance and Differentiation during Early and Late Stages of Rat Stomach Carcinogenesis

“…25,26) Previously we found that dendritic cells, which were stained with OX-62 mAb and which expressed MHC class I and II (MHC class II, Ii) genes, B7-1 and B7-2, appeared in the interstitial tissue of rat stomach pyloric mucosa after 14 days' MNNG exposure. 5,7) In the present study we confirmed gene expression of integrin αE2, known to be the antigen for OX-62 mAb, 11) and demonstrated gene expression of integrin β7, which is another unit of the integrin complex containing integrin αE2.…”

Appearance of Osteonectin‐expressing Fibroblastic Cells in Early Rat Stomach Carcinogenesis and Stomach Tumors Induced with N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine

“…Induction of pepsinogen-altered pyloric glands by MNNG 4,17) showed early changes in epithelial cells of pyloric mucosa. Thus, various changes are induced both in epithelial cells and interstitial tissue of pyloric mucosa in the early initiation stage and these changes continued until tumor development after 12 months.…”

“…4,5) Previously we found changes in gene expression in the initiation stage of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced rat stomach carcinogenesis by using FDD and we cloned MHC class II-associated invariant chain (Ii). 6) Then, we found that Ii was expressed in antigen-presenting dendritic cells, and we suggested the involvement of dendritic cell response in resistance to stomach carcinogenesis in a particular rat strain.…”