title: Experimental animal models of pancreatic carcinogenesis for prevention studies and their relevance to human disease.
abstract: Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5' CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.
authors.affiliation: Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. mtakahas@ncc.go.jp.
authors.forename: Mami
authors.initials: M
authors.lastname: Takahashi
authors.forename: Mika
authors.initials: M
authors.lastname: Hori
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mutoh
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagama