The effect of radiation-induced genotoxic stress on the expression of satellite II and satellite III repeats in breast and colon cancer cells

Pericentric human satellite II (HSATII) and III (HSATIII) have been shown to be associated with stress response. Expression status of these satellite repeats has not yet been investigated under radiation-induced genotoxic stress. We evaluated the HSATII and HSATIII expression changes under genotoxic stress in cancer cells.

Cell line MCF-7 and cell line HCT-15 were irradiated with 2 and 5 Gy of ionizing radiation, and cell death rates, as a consequence of genotoxic stress, were determined by flow cytometry. The expression of HSATII and HSATIII expressions was assessed by RT-qPCR.

Radiation exposure induced a considerable level of cell death in a dose-dependent manner in both cell types. Compared to untreated cells, HSATII expression declined in MCF-7 cells which were exposed to 2 and 5 Gy radiation, respectively. In HCT-15 cells, the effect of radiation on the HSATII expression was not unified; only higher radiation dose led to a decrease of HSATII expression while 2 Gy increased HSATII expression. The effect of radiation on the HSATIII repeat expression was more pronounced in HCT-15 cells: in MCF-7 cells, HSATIII expression was decreased by 2- and 5-Gy, respectively (p=0.01). In the HCT-15 cells, the rates of HSATIII down-regulation were 3-fold and 2.8 fold by 2- and 5 Gy (p=0.0002 and p=0.02, respectively).

Our findings reveal that genotoxic stress induced by ionizing radiation is associated with a decrease in the expression of pericentric satellites and the expression status of HSATII in these conditions may be dose- and/or cellular context-specific.