title: Identification of mouse mutant cells exhibiting the plastic mutant phenotype.
abstract: The initial processes involved in radiation carcinogenesis have not been clearly elucidated. We isolated mouse mutant cells exhibiting plasticity in their mutation phenotypes. These mutant cells were originally isolated from an irradiated cell population as 6-thioguanine resistant (6TGR) mutants that were deficient in hypoxanthine phosphoribosyl transferase (Hprt, E.C.2.4.2.8) activity at the frequency of approximately 6.2 x 10(-5). Approximately 10% of 6TGR cells showed plasticity in their mutant phenotypes and reverted to HAT-resistant (HATR), which is Hprt-proficient, wild type phenotype. Eventually we identified the plastic mutants in the un-irradiated wild type cell population as well and found that ionizing irradiation enhanced the frequency of the plastic mutation approximately 24 times. Treatment with 5-aza-cytidine did not affect the plasticity of mutant phenotypes identified in this study, suggesting that DNA methylation was not involved in the plastic changes of the mutant phenotypes. The plastic mutant phenotype identified in our study is a new type of genomic instability induced by ionizing irradiation, and it is likely to be involved in one of the primary changes that occur in the process of radiation carcinogenesis, and may explain one element of carcinogenesis, which is composed of multi-stages.
authors.affiliation: Laboratory of Precancerous Mutation, Experimental Radiobiology for Children's Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Inage, Chiba, Japan. m_yam@nirs.go.jp
authors.forename: Masatake
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Fukutsu
authors.forename: Mari
authors.initials: M
authors.lastname: Sakagami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000528:radiation effects; D004587:Electrophoresis, Agar Gel; D042822:Genomic Instability / Q000187:drug effects / Q000528:radiation effects; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D019656:Loss of Heterozygosity; D051379:Mice; D016133:Polymerase Chain Reaction; D013866:Thioguanine / Q000494:pharmacology; D014965:X-Rays
chemical_list: D000964:Antimetabolites, Antineoplastic; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine