Radiation-Induced DNA Methylation Disorders: In Vitro and In Vivo Studies

Abstract—: Phenomenological aspects and mechanisms of DNA methylation disorders (changes in the total level of DNA methylation and in genome repetitive elements, locus-specific methylation disorders, loss of imprinting) induced by radiation in experimental studies in vitro and in vivo, as well as in the human organism, are considered. The results of evaluation of association between radiosensitivity of tumor cells and their epigenetic status are demonstrated. Although it was established that the radioresistant phenotype of such cells is associated with hypermethylation of promoters of multiple genes, the mechanism of this phenomenon is very complex, and a targeted effect on methylation is required to increase the damageability of tumor cells leading to their death. The association of induced changes in DNA methylation with manifestations of nontargeted radiation effects such as genomic instability and the “bystander” effect was detected. The potential significance of the study of changes in DNA methylation in irradiated individuals in order to detect individuals with premature aging and increased risk of the development of age-associated pathology is discussed.