Page 28 - SDIR5 Abstract book 21 12 2021.

RADIOBIOLOGY

Effects of Ionizing Radiation on DNA Methylation: From Experimental Biology to Clinical
Applications

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Jadranka Antic
1 Department of Endocrine Tumors, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical
Centre of Serbia, Serbia

Ionizing radiation (IR) is a ubiquitous environmental factor and a clinically important diagnostic and
treatment modality with genotoxic and epigenotoxic capabilities. DNA methylation is a key epigenetic
mechanism in the regulation of the proper expression of genetic information. Alterations in DNA
methylation may result in changes in gene expression or reactivation of repetitive elements (REs), and may
lead to genomic instability and the development of pathological states. Knowledge regarding the effects of
IR on DNA methylation is constantly growing. Radiation can cause changes in global DNA methylation and
the extent of radiation-induced alterations in DNA methylation is tissue-dependent. Radiation-induced
alterations in DNA methylation may differ between species and even among strains of the same species.
DNA hypermethylation-induced silencing of tumor-suppressor genes and hypomethylation-induced
activation of oncogenes have been described in almost all human cancers and are considered driving
mechanisms of carcinogenesis. Alterations in the DNA methylation status of REs often lead to their
reactivation and retrotransposition, and are documented in human cancers as well as in response to
environmental stressors. In vitro studies reported mostly sex-specific bystander effect – the loss of genomic
DNA methylation in both irradiated and bystander regions. The phenomenon of IR-induced alterations in
DNA methylation is undeniable, however our understanding on the functional outcomes is very limited.
Epigenetic modifications are not limited to DNA only, histone proteins can also undergo those
modifications. Recently, of particular interest is the possibility of dietary modulation of the DNA
methylation patterns, which may potentially be a promissing direction in radiation oncology. Key words:
DNA methylation; Genomic instabillity; Ionizing radiation

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