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• W2057857351 abstract "Purpose of this study was to investigate apoptotic effects of 10MV x-rays at high dose rate (2400 MU/min) combined with unconventional low total dose (50cGy) in malignant melanoma cells in vitro. Concurrently, the preservation of cell survival on normal melanocytes (HEM), keratinocytes (HEK) and stromal cells (HEF) and radio-sensitization using mitochondrial inhibitors were also studied. Cell growth condition and density of cells were optimized by customizing culture media, cell confluence and supplemental factors. The cells were radiated using a linear accelerator with 400 or 2400 MU/min dose rates and total doses from 25-100 cGy. Cell counting, Colony Assays, Mitotracker fluorescent and bright fileld imaging, and MTT assay were used to investigate mitochondrial respiration, cell proliferation and radio-resistant cell morphology. Genes involved in mitochondrial respiration, apoptosis, cell division and signaling were quantitatively analyzed by qRT-PCR. Mitochondrial inhibitors were used to block mitochondrial respiration in cells. The apoptosis in melanoma cells were 30% higher and normal melanocyte survival was preserved 80 % with 50cGy delivered at 2400 MU/min than 50cGy delivered at a dose rate of 400MU/min in vitro setting (p<0.005). qRT-PCR data confirmed significant upregulation of apoptosis genes (AIF, FAS, FASL, Casp 3, Casp8, Casp9, TP53) in cancer cells and DNA repair and cell proliferation genes (MSH2, CCND1,CCND2, MDM2, MDM4) in HEM, HEK and HEF. Cell counts showed 60% and 68% reduction at 7 days post-radiation for the aggressive metastatic cells (p<.0.001) and for sensitive cells, respectively. Colony assays demonstrated 30% more cell killing with 2400MU/min than 400 MU/min and preserved 75% normal primary cells. Dose rate 2400 MU/min caused higher mitochondrial respiration than 400 MU/min which was directly related to total dose of radiation delivered to cells. However, the respiratory chain genes (NDUFS2, UCRC, SDHC, ATPAF2) were down regulated, suggesting that the increased respiration activity after radiation was related to post-translational activation. Mitochondrial inhibition increased cell kill to 74% (p<0.005) with inhibitor O and to 83% with inhibitor R while HEM maintained 60% survival. 10 MV x-rays at high dose rate with low total dose (2400 MU/min|50cGy) significantly enhances radio-sensitivity of melanoma cells while reducing radio-toxicity on normal cells. Additionally, blocking mitochondrial respiration proportionately increases melanoma cell kill with this dose rate. Our model implicates potential novel radio therapeutic options and opens untested field of radiation therapy research." @default.
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• W2057857351 date "2014-09-01" @default.
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• W2057857351 title "Experimental Radiation (2400 MU/min/50cGy) In-Vitro Achieved Significant Increase in Apoptosis on Melanoma Cells With Superior Survival of Normal Cells When Compared to 400 MU/min" @default.
• W2057857351 doi "https://doi.org/10.1016/j.ijrobp.2014.05.2280" @default.
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