Photodynamic therapy is the main technique applied for surface carcinoma treatment. This technique employs singlet oxygen generated via a laser excited photosensitizer as a main damaging agent. However, prolonged sensitivity to intensive light, relatively low tissue penetration by activating light the cost of photosensitizer (PS) administration can limit photodynamic therapy applications. Early was reported singlet oxygen generation without photosensitizer induced by a laser irradiation at the wavelength of 1250-1270 nm. Here, we study the dynamics of oxidative stress, DNA damage, changes of mitochondrial potential, and mitochondrial mass induced by a laser at 1265 nm have been studied in HCT-116 and CHO-K cells. Laser irradiation of HCT-116 and CHO-K cells has induced a dose-dependent cell death via increasing intracellular reactive oxygen species (ROS) concentration, increase of DNA damage, decrease of mitochondrial potential, and reduced glutathione. It has been shown that, along with singlet oxygen generation, the increase of the intracellular ROS concentration induced by mitochondrial damage contributes to the damaging effect of the laser irradiation at 1265 nm.

We studied the effect of inhibition of mitochondrial voltage-dependent anion channels with DIDS on radiosensitivity and mitochondrial status of K562 leukemic cells. The number of apoptotic and necrotic cells, mitochondrial transmembrane potential, and mitochondrial mass were evaluated after irradiation of cells in doses of 4 and 12 Gy in the presence and absence of the inhibitor. Inhibition of mitochondrial voltage-dependent anion channels increased radiosensitivity of K562 cells by 50-70% and decreased both mitochondrial transmembrane potential and mitochondrial mass. Inhibitors of voltage-dependent anion channels are promising agents capable of improving the effectiveness of cancer radiotherapy.

The aim of the investigation was to study differential gene expression and signaling pathways activation in radioresistant and radiosensitive cancer cell lines.Materials and Methods. K562 radioresistant cancer cell line of chronic myeloleukosis, and HCT-116p53 (+/+), HCT-116p53 (-/-), Me45 radiosensitive cancer cell lines were used in the study. Transcriptome analysis was performed using Affymetrix DNA microarray HGU133A series. Original Gene Selector program was used for bioinformation analysis. Protein interaction networks were studied by means of online STRING 9.0 system. To range the genes according to the signaling pathways the PANTHER program and QIAGEN SABiosciences database were used. Quantitative activation of signaling pathways was calculated with the help of OncoFinder bioinformation algorithm.Results. Four genes (DAAM1, IFNAR2, PALLD, STK17A) were identified to increase their expression in radioresistant cell line and to decrease it in radiosensitive cell lines under radiation exposure. Three signal pathways -Wnt, Interferon and p53 -in which these genes are involved and which are common to the examined cell lines were found using PANTHER program. A significant difference in activation of these signaling pathways was discovered in radioresistant and radiosensitive cell lines.Conclusion. Based on the analysis of molecular interaction networks and signaling pathway activation it has been revealed that the greatest differences between radioresistant and radiosensitive cell lines are observed in the activity of Interferon and p53 signaling pathways. TP53 gene expression level is not associated with the activity of p53 signaling pathway. Comparison of gene expression changes and activation of signaling pathways allows us to suggest the expression of DAAM1, IFNAR2, PALLD genes as indicators of radioresistance under radiation exposure.

The dynamics of oxidative stress, DNA damage, changes in mitochondrial potential and mitochondrial mass are studied with the cancer cells of HELA line irradiated by a Raman laser at the wavelength of 1265 nm. It is demonstrated that Raman laser irradiation at this wavelength induces cell death causing an increase of the concentration of intracellular reactive oxygen species, an increase of DNA damage, and a decrease of mitochondrial potential and mitochondrial mass.