Modulation of Enzymes Involved in Folate Dependent One-carbon Metabolism by γ-radiation Stress in Mice

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The role of various enzymes in folate dependent one-carbon metabolism, which are involved in mobilizing the folate pool for DNA synthesis and the DNA methylation reaction, was investigated. Male Swiss mice (6 weeks old) were subjected to 2, 5 and 7 Gy total body γ-irradiation. The animals were killed at intervals of 24, 48, 72, 96, 120 and 192h and the livers were removed. Using a 12000×g supernatant of 10% tissue homogenate, the activities of dihydrofolate reductase, thymidylate synthase and methylenetetrahydrofolate reductase were determined. The profiles of these folate enzymes were correlated to DNA damage by monitoring p53 protein profile and by comet tail moment analysis. A significant increase in activity of dihydrofolate reductase and thymidylate synthase was observed up to 96h post-irradiation and the activity subsided thereafter, reaching control value after 192h. A sharp decline in methylenetetrahydrofolate reductase activity was observed until 192h after irradiation. Total folates declined by 54% after 96h following irradiation, and p53 protein concentration in nuclei increased after irradiation, proportionate to radiation dose, and subsided slowly. Thus results indicate a significant drop in total folate levels and rise in p53 protein concentration in the liver after total body γ-irradiation. It may appear that, under radiation stress conditions, levels of enzymes involved in one-carbon metabolism for DNA repair, are modulated up to a certain time interval, in a dose specific manner. It may also appear that the requirements of folate for nucleotide base synthesis seem to be met at the expense of other one-carbon transfer reactions.
日本放射線影響学会の論文

Modulation of Enzymes Involved in Folate Dependent One-carbon Metabolism by γ-radiation Stress in Mice

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