ARTICLE
TITLE

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

SUMMARY

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 ?-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 ?omet 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 theaction 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.

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