The impact of ionizing irradiation in vitro on the genome of peripheral blood lymphocytes of the asymptomatic carriers of the 5382insC mutation in the BRCA1 gene

M. Romanenko, D. Kurinnyi, O. Demchenko, S. Klymenko, S. Rushkovsky
Taras Shevchenko National University of Kyiv, Kyiv; National Scientific Center for Radiation Medicine of the NAMS of Ukraine, Kiev; National Scientific Center for Radiation Medicine of the NAMS of Ukraine, Kiev; National Scientific Center for Radiation Medicine of the NAMS of Ukraine, Kiev; Taras Shevchenko National University of Kyiv, Kyiv

Abstract


One of the hereditary factors affecting the development of breast and ovarian cancer is the 5382insC mutation in BRCA1 gene. But, nearly 15 % of carriers of this mutation do not manifest cancer during their lifetime. At present, the features of the development of spontaneous and induced genomic instability in asymptomatic carriers of BRCA1 mutations are studied insufficiently. The aim of the work was to evaluate the effect of the 5382insC BRCA1 mutation on the radiosensitivity of lymphocytes of individuals without an established oncopathology. The cultivation of blood lymphocytes obtained from 9 women (3 individuals with the 5382insC BRCA1 mutation without established oncopathology, and 6 conditionally healthy volunteers) was carried out. Some of the cultures were irradiated with γ-quanta (IBL-237C emitter, power 2.34 Gy/min) at a dose of 1.0 Gy before cultivation. For evaluation of the relative level of DNA damage the method of Сomet assay was applied. It was found that spontaneous level of DNA damage in cultures of lymphocytes of carriers of the BRCA1 5382insC mutation was statistically significantly (p < 0.01) higher than in the control group. After exposure to ionizing radiation for lymphocyte cultures of individuals with BRCA1 5382insC mutation, a decrease (p < 0.01) in the level of cells with a high degree of DNA damage was observed while the apoptotic activity was found to be increased (p < 0.01). It has been suggested that an increase in the elimination of damaged cells due to apoptotic activity in response to the
action of genome-damaging factors is one of the effective mechanisms that can significantly reduce the likelihood of cancer in asymptomatic carriers of the BRCA1 gene mutations.

Keywords


BRCA1 gene, Comet assay, apoptosis, peripheral blood lymphocytes, radiation, DNA damage

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Received: 15.10.2020

Revised: 16.11.2020

Signed for the press: 16.11.2020




DOI: http://dx.doi.org/10.17721/1728_2748.2020.83.55-61

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