title: Review: Animal models of N-Methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials.
abstract: N-Methyl-N-nitrosourea (MNU) is a direct-acting alkylating agent that interacts with DNA. Accumulation of mutations may enhance cancer risk in target organs or cause cell death in susceptible tissues or cells when excessive DNA damage is not repaired. MNU targets various organs in a variety of animal species. MNU-induced carcinogenesis can be used as organ-specific animal models for human cancer, and MNU has been most extensively utilized for the induction of mammary cancer in rats. MNU-induced rat mammary tumors possess many similarities to those of human breast cancer, and the model is utilized for screening cancer modulators. MNU-induced cell disruption is also seen in several organs and tissues, especially when MNU is applied before maturity. However, photoreceptor cells in adults are highly sensitive to MNU, which causes cell death due to apoptosis. MNU-induced photoreceptor apoptosis mimics human retinitis pigmentosa and can be used for studies of therapeutic intervention. In this review, the targets of MNU in various animal species are described, and special emphasis is given to therapeutic trials against MNU-induced mammary cancer and retinal degeneration in animal models.
authors.affiliation: Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan. tsubura@takii.kmu.ac.jp
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
authors.forename: Yen-Chang
authors.initials: YC
authors.lastname: Lai
authors.forename: Hisanori
authors.initials: H
authors.lastname: Miki
authors.forename: Tomo
authors.initials: T
authors.lastname: Sasaki
authors.forename: Norihisa
authors.initials: N
authors.lastname: Uehara
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000473:pathology; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008770:Methylnitrosourea / Q000737:chemistry / Q000633:toxicity*; D016296:Mutagenesis; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009536:Niacinamide / Q000627:therapeutic use; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D012174:Retinitis Pigmentosa / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy; D035703:Therapies, Investigational
chemical_list: D000477:Alkylating Agents; D002273:Carcinogens; D009536:Niacinamide; D008770:Methylnitrosourea