title: Long-term administration of the fungus toxin, sterigmatocystin, induces intestinal metaplasia and increases the proliferative activity of PCNA, p53, and MDM2 in the gastric mucosa of aged Mongolian gerbils.
abstract: OBJECTIVE
  The causal agents of gastric cancer could include fungus toxins. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. We investigated the effects of ST on the stomach tissues of Mongolian gerbils.
  
  
  METHODS
  Seventy-five-week-old male Mongolian gerbils received ST ad libitum at a concentration of 0 ppb (non-treated, n = 11), 100 ppb (n = 7), or 1000 ppb (n = 13) dissolved in drinking water for a period of 24 weeks. After administration, we tested the histopathological changes and immunostaining for proliferating cell nuclear antigen (PCNA), p53, and MDM2 expression.
  
  
  RESULTS
  We investigated the histopathological changes and determined the incidence of histopathological changes in animals with various gastric diseases after ST administration at a dose of 0 ppb (non-treated control), 100, or 1,000 ppb as follows: firstly, indices for gastritis were 18.2, 100, and 100%, those for erosion events were 9.1, 100, and 92.3%, and those for polyps were 0, 71.4, and 61.5%, respectively. These incidences in the ST-administered groups (100 or 1000 ppb) showed significant increases compared with those in the non-treated control group. And, lastly, indices for intestinal metaplasia were 0, 100, and 15.4%, respectively. Furthermore, immunostaining for PCNA, p53, and MDM2 expression showed significantly greater rates in the ST-administered groups (100 or 1000 ppb) than in the non-treated control group.
  
  
  CONCLUSIONS
  The histopathological and immunohistopathological findings of this study indicate that ST exerts a marked influence on gastric mucus and gland cells, showing dominant gastritis, erosion events, polyps, and intestinal metaplasia in these animals.
authors: Department of Matrix Medicine, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu, Oita, 879-5593, Japan. e21501@oita-u.ac.jp
authors: Masahiro
authors: M
authors: Kusunoki
authors: Junichi
authors: J
authors: Misumi
authors: Tatsuo
authors: T
authors: Shimada
authors: Kazuo
authors: K
authors: Aoki
authors: Noritaka
authors: N
authors: Matsuo
authors: Hideaki
authors: H
authors: Sumiyoshi
authors: Takeshi
authors: T
authors: Yamaguchi
authors: Hidekatsu
authors: H
authors: Yoshioka
mesh_terms: D000818:Animals; D001230:Aspergillus / Q000187:drug effects; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000139:chemically induced* / Q000382:microbiology / Q000473:pathology; D005849:Gerbillinae; D008297:Male; D008679:Metaplasia / Q000139:chemically induced / Q000382:microbiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013241:Sterigmatocystin / Q000008:administration & dosage / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D013241:Sterigmatocystin; D051736:Proto-Oncogene Proteins c-mdm2