Animal models of stomach carcinogenesis.
Although incidences of stomach cancer have decreased over the past several decades, the disease remains an important public health problem. To identify pathological and molecular biochemical mechanisms, various experimental animal models have been established in rats and mice with chemical carcinogens including N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU). Helicobacter pylori(H. pylori) is one of the most important factors for human stomach disorders, including neoplasia, and the H. pylori-infected and carcinogen-treated Mongolian gerbil (MG) has proven very useful for analyses of underlying processes. The findings with this model support the hypothesis that intestinal metaplasia is important not as a precancerous lesion but rather as a paracancerous condition and that intestinalization of stomach cancer progresses with chronic inflammation. Furthermore, dose-dependent enhancing effects of salt on stomach carcinogenesis could be demonstrated in MGs treated with MNU and H. pylori modifying surface mucous gel layer. H. pylori itself only causes chronic inflammation and acts as a promoter of stomach carcinogenesis in experimental models. Based on the precise pathological diagnosis of stomach lesions such as noncancerous heterotopic proliferative glands (HPG) and adenocarcinomas, a basis for understanding mechanisms of carcinogenesis has been established on which chemoprevention can be modeled.
Tsukamoto
Tetsuya
T
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan. ttsukamt@aichi-cc.jp
Mizoshita
Tsutomu
T
Tatematsu
Masae
M
D000818:Animals; D000071616:CDX2 Transcription Factor; D051546:Cyclooxygenase 2 / Q000502:physiology; D004195:Disease Models, Animal; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D008679:Metaplasia; D011230:Precancerous Conditions / Q000473:pathology; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000145:classification / Q000209:etiology* / Q000473:pathology; D015534:Trans-Activators / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D017673:Sodium Chloride, Dietary; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C084010:pancreatic and duodenal homeobox 1 protein; D051546:Cyclooxygenase 2