RADIORESISTANCE MECHANISMS OF SIDE POPULATION CELLS IN MOUSE MELANOMA CELL LINE B16
O.N. Matchuk,1 Zamulaeva I. A., Kovalev O. A., Saenko A.S.
Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russia;
1 e-mail: matchyk@mail.ru
As it was shown by us earlier, side population (SP) cells are more resistant to the low-LET radiation than the other part of mouse melanoma B16 cells (Matchuk et al., 2012).
The aim of our research was finding some mechanisms of radioresistance, therefore we analyzed SP and nonSP cell cycle distribution, spontaneous and radiation induced DNA
double-strand breaks (number of γH2AX foci) and intracellular NO concentration. The results indicate that SP cells have significantly less DNA double-strand breaks
after irradiation at dose of 3 Gy than nonSP cells (24,4 vs 40,3, accordingly, p<0,05 Mann-Whitney U criterion). SP cells are more quiescent compared to nonSP
(G1/G0)-fraction is 85 % vs 39 %, accordingly, p<0,01 Mann-Whitney U criterion). Most SP cells reside in G2/M phases (61 %),
believed to be rather radiosensitive. Thus, the difference of SP and nonSP cells radiosensitivity can be partly explained by peculiarities of cell cycle distribution. NO concentration is
1.5 times higher in SP than nonSP cells (p<0,05 Mann-Whitney U criterion); since it is known that NO inhibits apoptosis, being one of the mechanisms of genetic stability maintanance,
greater number of spontaneous DNA double-strand breaks in SP cells is unsurprising (p<0,05 Mann-Whitney U criterion). The above-listed results explain considerably the higher
resistance of SP cells to the action of low-LET radiation in comparison with other melanoma B16 cells. Further study of this question can become the basis for development of tools
to target SP cells and, ultimately, more effective cancer treatment.
Key words: side population, melanoma B16, cell cycle, H2AX foci, nitric oxide
| Back
| Contents
| Main |
