Shemetun O. Cytogenetic aspects of the development and persistence of radiation-induced bystander effect in human somatic cells

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0519U001772

Applicant for

Specialization

  • 03.00.15 - Генетика

31-10-2019

Specialized Academic Board

Д 26.562.02

State Institution "National Research Centre For Radiation Medicine of National Academy of Medical Sciences of Ukraine"

Essay

The cytogenetic aspects of the development of radiation-induced bystander effect (RIBE) in human somatic cells was investigated in the dissertation and the concept of its development, persistence and modification was formulated. It was shown that the model system for the study of RIBE should consist of of co-cultured irradiated (in vitro / in vivo) and non-irradiated blood lymphocytes, differing in cytogenetic markers (Y, XX, morphological variants of somatic chromosomes), which are detected using GTG staining. The development of the RIBE in the un-irradiated human blood lymphocytes cultivated in mixed cultures with lymphocytes irradiated in vitro at doses of 0.25 and 1.00 Gy have been established. RIBE was manifested of the increased induction of chromatid type aberrations (CTA). The level of CTA in the bystander cells does not depend on their background frequency and the and the dose of radiation exposure the targeted cells population. The persistence of RIBE in the blood lymphocytes of the the liquidation of the consequences of the Chornobyl accident (LCCHA) was established for 19 years. The clastogenic activity of LCCHA blood was shown in the long term after the action of ionizing radiation, which caused an increase in the frequency of CTA in intact cells. The possibility of genomic instability persistence due to the RIBE during four mitotic divisions at 120-hour co-cultivation of non-irradiated cells with blood lymphocytes, irradiated in vitro at a dose of 0.25 Gy was proven. The induction of RIBE (abscopal effect) and the increase in the frequency of CTA in the lymphocytes of individuals exposed of 131I to the thyroid gland was established. The interindividual differences and the peculiarities of development of the RIBE in human blood lymphocytes depending on age were established. The interindividual differences and the peculiarities of development of the RIBE in human blood lymphocytes in persons aged 12–102 depending on age were established. The absence of induction RIBE in persons aged 90–102 years was shown. Modification of RIBE with the help of antioxidant drug containing water soluble forms of vitamins E, C and A was made. After the adding of this drug at a concentration of 40.00 μg / ml to the mixed culture of irradiated at a dose of 1.00 Gy and un irradiated cells BE was not inducted. The influence of un-exposed cells on irradiated lymphocytes (rescue effect) during their 120-hour co-cultivation was established. The decrease in the level of chromosome aberrations in the irradiated cells was shown.

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