BioScience Trends. 2010;4(6):312-317. (DOI: )

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.

Yamauchi M, Fukutsu K, Sakagami M, Miyazaki T, Yamada Y

As we previously reported, we isolated and examined mouse mutant cells exhibiting phenotypic plasticity. Approximately 10% of 6-thioguanine resistant (6TG^R) cells derived from the irradiated cell population exhibited phenotypic plasticity and reverted to wild type HAT resistance (HAT^R). 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^R 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.

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