Assessing the Association of the Degree of DNA Methylation and the Frequency of Chromosomal Aberrations in Human Lymphocytes in a Single Irradiation of Blood in vitro

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Abstract

The most sensitive biomolecule under radiation exposure is DNA, whose damage manifests itself in the form of chromosomal aberrations (CA). The processes of DNA methylation, which are involved in the regulation of gene expression, replication, DNA repair, etc., are also affected by gamma radiation. The aim of the study was to evaluate the relationship between the degree of DNA methylation and the frequency of CA after acute in vitro irradiation of human blood lymphocytes with gamma radiation. The study involved 10 conditionally healthy workers of the Siberian Chemical Combine, in whose blood lymphocytes the degree of methylation of CpG-dinucleotides (wide-genome bisulfite sequencing, XmaI-Reduced representation bisulfite sequencing – XmaI-RRBS) and the frequency of CA (cytogenetic study) after acute in vitro blood irradiation with doses of 0 and 1.5 Gy were evaluated. After acute exposure to gamma radiation in lymphocytes, the frequency of aberrant cells, dicentric chromosomes, chromatid and chromosomal fragments increased. Correlation analysis of the status of CpG-dinucleotide methylation and the frequency of CA revealed changes in the degree of methylation of 97 genes, which strongly correlated positively (56 genes) or negatively (41 genes) with an increased frequency of CA. A primary genome-wide screening of genes whose methylation is correlates with a high frequency of CA was carried out. Many of the identified genes are promising as potential markers of radiation exposure and to study the mechanisms of formation of radiosensitivity of the body and radioresistance of tumors during radiation therapy.

About the authors

O. S. Tsymbal

Seversk Biophysical Research Center of the Federal Medical-Biological Agency

Author for correspondence.
Email: olga-tsymbal@mail.ru
Russia, 636013, Seversk

I. V. Milto

Seversk Biophysical Research Center of the Federal Medical-Biological Agency; Siberian State Medical University

Email: olga-tsymbal@mail.ru
Russia, 636013, Seversk; Russia, 634050, Tomsk

N. V. Litviakov

Seversk Biophysical Research Center of the Federal Medical-Biological Agency; Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: olga-tsymbal@mail.ru
Russia, 636013, Seversk; Russia, 634009, Tomsk

Zh. А. Startseva

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: olga-tsymbal@mail.ru
Russia, 634009, Tomsk

A. I. Kalinkin

Research Centre for Medical Genetics

Email: olga-tsymbal@mail.ru
Russia, 115478, Moscow

V. O. Sigin

Research Centre for Medical Genetics

Email: olga-tsymbal@mail.ru
Russia, 115478, Moscow

A. F. Nikolaeva

Research Centre for Medical Genetics

Email: olga-tsymbal@mail.ru
Russia, 115478, Moscow

E. V. Bronikovskaya

Seversk Biophysical Research Center of the Federal Medical-Biological Agency

Email: olga-tsymbal@mail.ru
Russia, 636013, Seversk

D. S. Isubakova

Seversk Biophysical Research Center of the Federal Medical-Biological Agency

Email: olga-tsymbal@mail.ru
Russia, 636013, Seversk

R. M. Takhauov

Seversk Biophysical Research Center of the Federal Medical-Biological Agency; Siberian State Medical University

Email: olga-tsymbal@mail.ru
Russia, 636013, Seversk; Russia, 634050, Tomsk

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Copyright (c) 2023 О.С. Цымбал, Д.С. Исубакова, Е.В. Брониковская, А.Ф. Николаева, В.О. Сигин, А.И. Калинкин, Ж.А. Старцева, Н.В. Литвяков, И.В. Мильто, Р.М. Тахауов

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