Radiosensitization of Cancer Cells by 5-Selenocyanato- and 5-Trifluoromethanesulfonyl- Derivatives of 2'-deoxyuridine.

Abstract

Radiation chemical studies together with theoretical calculations have confirmed that 5-selenocyanato-2'-deoxyuridine (SeCNdU) and 5-trifluoromethanesulfonyl-2'-deoxyuridine (OTfdU) undergo dissociation induced by an excess electron attachment and established these nucleosides as potential radiosensitizers. Here, the sensitizing properties of SeCNdU and OTfdU at the cellular level have been verified to determine whether these analogs can effectively enhance ionizing radiation-induced cell death. The cytotoxicity and radiosensitizing activity of the tested compounds were examined in breast (MCF-7) and prostate (PC3) cancer cells. The viability of cells treated with the analogs was tested using the MTT assay. The clonogenic assay was used to quantify reproductive cell survival after treatment of the compounds with ionizing radiation. For preliminary investigation of the mechanisms of potential radiosensitization by the derivatives, cell cycle phase distribution and histone H2AX phosphorylation as a marker of DNA strand breaks were assessed using flow cytometry. The results show the radiosensitizing properties of SeCNdU on the MCF-7 line, with a dose enhancement factor of 1.6. The same derivative had no effect on the PC3 line. Radiosensitization was also associated with an increase in histone H2AX phosphorylation, which correlates with the number of DNA double breaks. This derivative also slightly influenced distribution of cells through the cell cycle. The OTfdU derivative showed no biological effect on either of the tested lines. In conclusion, SeCNdU treatment enhanced the radiosensitivity of breast cancer cells in a manner associated at least partially with double-strand break formation. OTfdU had no radiosensitizing effect against prostate and breast cancer lines.