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O. V. Shemetun, O. A. Talan, O. B. Dibska
State Institution «National Research Center for Radiation Medicine, Hematology and Oncology of the National Academy of Medical Sciences of Ukraine», 53 Yuriia Illienka St., Kyiv, 04050, Ukraine
PERSISTENCE OF GENOMICAL INSTABILITY DUE TO THE DEVELOPMENT OF THE TUMOR-INDUCED BYSTANDER EFFECT IN HUMAN SOMATIC CELLS
Objective: to establish the level of chromosome aberrations in human peripheral blood lymphocytes during the
development of a tumor-induced bystander effect over several mitotic divisions.
Materials and Methods. Material: human peripheral blood lymphocytes; human non-small cell lung cancer A-549
cell culture. Method: cytogenetic analysis of uniformly stained human peripheral blood lymphocyte chromosomes
to determine the frequency of all types of aberrations.
Results. In human peripheral blood lymphocytes after long-term (120-hour) cultivation with the addition of conditioned medium from human non-small cell lung cancer A-549 cells, an increase in the level of chromosome aberrations was registered compared to the control: from 1.90 to 3.40 per 100 cells in the first mitosis; from 2.00 to 3.60
per 100 cells in the second; from 1.70 to 3.10 per 100 cells in the third; and from 1.50 to 2.80 per 100 cells in the
fourth cell division (p < 0.05). The increase in chromosomal instability occurred due to an increase in the frequency of single fragments: from 0.70 to 2.20 per 100 cells in the first mitosis; from 1.00 to 2.10 per 100 cells in the
second; from 0.90 to 2.00 per 100 cells in the third; and from 1.10 to 2.40 per 100 cells in the fourth cell division
(p < 0.05). The frequencies of chromosomal-type aberrations (acentric paired fragments, abnormal monocentrics)
showed no significant difference from the corresponding control levels (p > 0.05) during the observation period.
Dicentric chromosomes were not registered.
Conclusions. Persistence of genomic instability due to the development of a tumor-induced bystander effect was
established in peripheral blood lymphocytes of healthy individuals after four cell divisions of cultivation with a conditioned medium from human non-small-cell lung cancer A-549 cells. Its cytogenetic manifestation was an increase
in the frequency of chromosome aberrations due to chromatid-type damage. The frequencies of chromatid-type
aberrations (single fragments) exceeded the corresponding controls and did not differ significantly between mitotic divisions. The development of the tumor-induced bystander effect did not influence the induction of chromosomal-type aberrations (acentric fragments, abnormal monocentrics, dicentric chromosomes), whose levels did not differ significantly from the controls.
Key words: tumor-induced bystander effect; human peripheral blood lymphocytes; persistence; genomic instability; chromosome aberrations.
Problems of Radiation Medicine and Radiobiology.
2025;30:284-298. doi: 10.33145/2304-8336-2025-30-284-298
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