Modulation of DNA Methyltransferase 1 Profile by γ-lrradiation Followed by Methyl Donor Starvation

Abstract

Abstract Role of one-carbon transfer agents methyl donors namely folate, choline and methionine in DNA methylation has been the subject of extensive investigation. The methylation pattern of DNA is established during embryogenesis and is subsequently maintained by maintenance methylation activity of the enzyme DNA methyltransferase 1 (dnmt 1). Ionizing radiation is known to extensively damage the DNA. Folate, a water-soluble vitamin, is known to contribute towards repair of damaged DNA due to its role in synthesis of nucleotide base adenine, guanine and thymidylate. Sufficient dietary availability of methyl donors, therefore, might have ability to modify radiation effects. In the present study, modifications in levels of dnmt 1 by g-irradiation followed by methyl donor starvation were observed. Experiments showed a dose and methyl donors starvation dependent attenuation in dnmt 1 activity. Attenuation of dnmt 1 activity was most significant for diet deprived of all the three methyl donors. Ionizing radiation and methyl donor deficiency were observed to act synergistically towards inhibiting dnmt 1 activity. Present results suggested possibility of interaction among folate, methionine and choline deficiency to potentate symptoms of ionizing radiation stress. These enzymatic modifications might contribute to altered DNA methylation after chronic feeding of methyl donor free diets after gamma irradiation. These results suggest that dietary availability of methyl donors and γ-radiation stress might significantly alter the dnmt 1 profile.