Helicobacter pylori, N-methyl-N'-nitro-N'-nitrosoguanidine, and bile modulate gastric cell kinetics in experimental cancer.
Helicobacter pylori infection is a risk factor for gastric cancer. How the bacterium contributes to this process is still unclear. We present a new Wistar rat model that was used to evaluate the effect of H. pylori on early preneoplastic events as judged from epithelial cell turnover and histopathological changes. One hundred and four rats were colonized with H. pylori and exposed MNNG (N-methyl-N'-nitro-N'-nitrosoguanidine) and/or taurocholic acid. Inflammation, goblet cell-like metaplasia, atrophy, dysplasia, and adenocarcinoma were scored in a blinded manner. Apoptotic cells were counted after staining with terminal uridine deoxynucleotidyl nick end labeling, and epithelial cell proliferation was determined by means of the Ki-67 labeling index. No early tumor enhancement with H. pylori could be found in ordinary histology. However, H. pylori significantly enhanced the epithelial cell proliferation compared with the control group, and the combination with taurocholic acid appeared to have a synergistic effect. MNNG significantly increased the normal gastric epithelial apoptosis. This increase was reduced in antral mucosa with H. pylori infection. The findings suggest that H. pylori, especially when combined with bile. has an influence on cell kinetics, contributing to the development of gastric cancer. The reduced apoptosis of MNNG also observed in infected animals indicates a dual function of H. pylori.
Loogna
P
P
Department of Surgery, Orebro Medical Centre Hospital, Sweden.
Franzén
L
L
Sipponen
P
P
Domellöf
L
L
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects* / Q000382:microbiology*; D016481:Helicobacter Infections / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D013656:Taurocholic Acid / Q000494:pharmacology*
D002273:Carcinogens; D019394:Ki-67 Antigen; D008769:Methylnitronitrosoguanidine; D013656:Taurocholic Acid