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Identification of mouse mutant cells exhibiting plastic mutant phenotype II; Ionizing radiation-induced mutant phenotype plasticity is not dependent on DNA methylation of the hypoxanthine phosphoribosyl transferase gene in mouse FM3A cells.
MedLine Citation:
PMID:  21248429     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
As we previously reported, we isolated and examined mouse mutant cells exhibiting phenotypic plasticity. Approximately 10% of 6-thioguanine resistant (6TG<sup>R</sup>) cells derived from the irradiated cell population exhibited phenotypic plasticity and reverted to wild type HAT resistance (HAT<sup>R</sup>). Similar mutant cells were also identified in an un-irradiated wild type cell population, but at a lower frequency. Ionizing irradiation enhanced the frequency of the plastic mutation approximately 24 times in our experiments. Treatment with 5-aza-cytidine did not affect phenotypic plasticity. In this study, we further performed detailed molecular analysis of the promoter region of the hypoxanthine phosphoribosyl transferase (Hprt) gene. The analysis revealed that most cytidine residues were not methylated, even in 6TG<sup>R</sup> mutant cells, in which Hprt activity must be down-regulated. These results suggested that DNA methylation was not involved in mutant phenotype plasticity, a new type of genomic instability induced by ionizing radiation. Plasticity in gene regulation may play an important role in radiation carcinogenesis, which is a multiple-stage process.
Authors:
M Yamauchi; K Fukutsu; M Sakagami; T Miyazaki; Y Yamada
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Bioscience trends     Volume:  4     ISSN:  1881-7823     ISO Abbreviation:  Biosci Trends     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-01-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101502754     Medline TA:  Biosci Trends     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  312-7     Citation Subset:  IM    
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;
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