This group of tumor cells declined in numbers while the control oligo treated tumor cells, though exposed to the same dose of 3 Gy, technical support continued to replicate. These results suggest enhanced inhibition of mammary tumor cells treated with T oligo and 3 Gy radiation. The inhibition of growth after 40 uM T oligo and 3 Gy IR was more pronounced than in cells treated with control oligo or diluent Inhibitors,Modulators,Libraries alone and 6, 9 or 12 Gy. The clonogenic cell survival assay is the gold standard to measure the Inhibitors,Modulators,Libraries radiosensitivity of cells. To determine if T oligo can sensitize mammary tumor cells to radiation, tumor cells pretreated for 24 hours with T oligo, con trol oligo or medium alone were irradiated with indi cated doses of radiation and then the surviving fraction of cells was deter mined.

As shown in Figure 1c, the survival curve of tumor cells treated with T oligo and IR shifted to the left considerably compared with those treated with con trol oligo or medium Inhibitors,Modulators,Libraries and 3 Gy, suggesting significant radiosensitization of tumor cells by T oligo. The mean lethal dose for tumor cells treated with radiation plus T oligo, control oligo or medium alone was 1. 46, 2. 98 and 3. 36 Gy, respectively. The survival fraction at 2 Gy for tumor cells treated with T oligo and radiation are comparable to those of cell lines considered to be radiosensitive. Thus pretreatment with T oligo increases the sensitivity of tumor cells to radiation and the combined treatment with T oligo and radiation can lead to cell growth arrest and or death as demonstrated by the clonogenic assay.

Mechanism of T oligo induced hypersensitivity to radiation To investigate potential mechanisms Inhibitors,Modulators,Libraries behind radiosensi tization of tumor cells Inhibitors,Modulators,Libraries by T oligo, we next examined the levels of nuclear foci containing phosphorylated H2AX, a modification that occurs at sites of DNA breaks. Figure 2a shows representative immuno fluorescent images of gH2AX foci in treated mammary tumor cells. Increased numbers of gH2AX foci per cell were observed in tumor cells treated with T oligo and 3 Gy IR at every time point after radiation compared with those in tumor cells treated with control oligo or med ium alone and 3 Gy. The difference in gH2AX focus number between tumor cells treated with T oligo and IR and control groups at 1, 3, 6 and 24 hours is statistically significant. These results suggest that T oligo enhances radiation induced DNA damage signal and or delays DNA repair, although T oligo alone is known to transiently induce gH2AX foci at telomeres in the apparent absence of double strand Carfilzomib Proteasome DNA breaks or other damage. We next compared DNA fragmentation in tumor cells treated with T oligo and 3Gy IR using the comet assay.