title: Long-term Treatment with Sterigmatocystin, a Fungus Toxin, Enhances the Development of Intestinal Metaplasia of Gastric Mucosa in Helicobacter pylori-infected Mongolian Gerbils.
abstract: BACKGROUND
  Helicobacter pylori is a human gastric carcinogen. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. Cytotoxin-vacuolation toxin A (VacA) present in supernatants of H. pylori suspensions can cause gastritis and ulcer. The aim of this study was to examine the effects of H. pylori, ST and VacA in Mongolian gerbils.
  
  
  METHODS
  Male Mongolian gerbils (n = 196) were treated with H. pylori supernatants (10 ml/1000 mg) mixed with diet or inoculated intragastrically with H. pylori alone or with ST (100 or 1000 ppb), and then killed 27 months later. Gastric tissue sections were stained with haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5) and with immunostaining for PCNA and p53 expression.
  
  
  RESULTS
  In H. pylori-infected gerbils, the normal mucosa was replaced by hyperplastic epithelium. Severe gastritis, cystic dilatation of gastric glands, hyperplastic polyps and intestinal metaplasia were observed. In H. pylori + ST (1000 ppb) gerbils, intestinal metaplasia was significantly more frequent than in H. pylori alone animals. No pathological changes were observed in the H. pylori supernatant group. Osseous metaplasia was observed in the H. pylori + ST (100 ppb) group. Serum gastrin levels of the H. pylori + ST (1000 ppb) group were significantly higher than those of the other groups. PCNA labelling index and p53 index of infected gerbils were significantly higher than those of uninfected groups.
  
  
  CONCLUSIONS
  H. pylori causes gastritis, ulcer and intestinal metaplasia. ST enhances the development of intestinal metaplasia and increases gastrin levels in H. pylori-infected Mongolian gerbils.
authors.affiliation: a Second Dept. of Public Health and Hygiene , Oita Medical University , Oita , Japan ; Dept. of Pharmacology , University of Tennessee Medical Center , Memphis , TN , USA.
authors.forename: F
authors.initials: F
authors.lastname: Ma
authors.affiliation: a Second Dept. of Public Health and Hygiene , Oita Medical University , Oita , Japan ; Dept. of Pharmacology , University of Tennessee Medical Center , Memphis , TN , USA.
authors.forename: J
authors.initials: J
authors.lastname: Misumi
authors.affiliation: a Second Dept. of Public Health and Hygiene , Oita Medical University , Oita , Japan ; Dept. of Pharmacology , University of Tennessee Medical Center , Memphis , TN , USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.affiliation: a Second Dept. of Public Health and Hygiene , Oita Medical University , Oita , Japan ; Dept. of Pharmacology , University of Tennessee Medical Center , Memphis , TN , USA.
authors.forename: K
authors.initials: K
authors.lastname: Aoki
authors.affiliation: a Second Dept. of Public Health and Hygiene , Oita Medical University , Oita , Japan ; Dept. of Pharmacology , University of Tennessee Medical Center , Memphis , TN , USA.
authors.forename: M
authors.initials: M
authors.lastname: Kudo
keywords: Gastrin level; Helicobacter pylori; Mongolian gerbils; intestinal metaplasia; osseous metaplasia; sterigmatocystin