Peculiarities of modifying effects of chemical agents on the formation of radiation-induced damage in genetic apparatus of human cells

Pylypchuk O.P., Demchenko O., Domina E.A.

O. Pylypchuk, O. Demchenko, E. Domina

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine

Introduction: Accumulation of chromosomal aberrations in cells is potentially oncogenic; thus, ionizing radiation (IR), which induces such changes, is a carcinogenic factor. Combination of chemical agents, IR with different mechanisms of action on human genome still has to be elucidated. Aim: To determine and provide a comparative analysis of combined action of irradiation, co-mutagens, and mutagens using cell culture of human peripheral blood lymphocytes (LPB). Materials and Methods: Culture of LPB, metaphase chromosomes cytogenetic analysis after ionizing radiation in the range of 0.3–2.0 Gy; co-mutagen verapamil (V) treatment in different concentrations (1.5–4.0 µg/ml); mutagen — nitrozotiol (GSNO) treatment as a transport form of nitrogen oxide (0.25–1.0 mM/ml) (experiments in vitro, two cell generations after irradiation). Results: A phenomenon of co-mutagenesis, which stands for combined action of radiation exposure (0.3–2.0 Gy) and V treatment (1.5–4.0 µg/ml of blood), on the level of chromosomal aberrations in PBL has been established. It has been shown that V at concentration of 4.0 µg per ml of blood increased the damaging effect of low doses of radiation up to 1.5-fold. Frequency of chromosomal aberrations (radiation markers) became higher with the increase of concentration of co-mutagen V (1.5–4.0 µg/ml). Combined treatment of PBL with IR and mutagen GSNO (two cell generations after irradiation) resulted in synergistic effect which enhanced the additive effect due to chromosomal aberrations, which are known to be the genetic markers of chemical agents’ action. Proliferative potential of PBL decreased more than 60% under IR and GSNO treatment. Level of aberrations of the chromatid type rose with increasing concentrations of GSNO (0.5 mM to 1.0 mM) by 3-fold. Combination of low doses of radiation and V inhibited cell proliferative potential, but increasing of exposure dose did not alter this effect. Conclusions: Increase in concentration of co-mutagens in combination with ionized radiation enhances chromosomal aberrations in PBL. Moreover, proliferative potential of PBL decreases under IR and GSNO treatment. Low doses of radiation and V inhibit cell proliferative potential; nevertheless, it remained unchanged when the doses of radiation were increased.

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