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 thedevelopment of a tumor induced bystander effect over several mitotic divisions.

[MATERIAL] human peripheral blood lymphocytes; human nonsmall cell lung cancer A549cell culture.

[METHOD] cytogenetic analysis of uniformly stained human peripheral blood lymphocyte chromosomesto determine the frequency of all types of aberrations.

[RESULTS] In human peripheral blood lymphocytes after longterm (120hour) cultivation with the addition of conditioned medium from human nonsmall cell lung cancer A549 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 3.60per 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 thefourth 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 thesecond; 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 nonsmall cell lung cancer A549 cells. Its cytogenetic manifestation was an increase in the frequency of chromosome aberrations due to chromatidtype damage. The frequencies of chromatidtypeaberrations (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.