A quantitative evaluation of DNA damage from irradiation of feline oral squamous cell carcinoma cells
Abstract
Feline oral squamous cell carcinoma is a locally invasive neoplasm that continues to carry a poor prognosis despite advances in multimodality oncologic treatment. Location, completeness of surgical excision or complete response to radiation therapy at day 30 have been shown to be predictive of survival. Tolerable treatment with radiation and concurrent chemotherapy has been described, but the ideal radiation protocol has not been determined. Though risk factors and prognostic indicators have been identified, there is no test to predict outcome prior to treatment. Three feline oral squamous cell lines (SCCF1, SCCF2, SCCF3) were used to investigate the potential of the alkaline comet assay to predict radiosensitivity. The three cell lines were irradiated with 6 MV photons and initial DNA damage using percent DNA in the comet tail and comet tail moment were plotted against all doses (0 - 9 Gy) for each cell line. There was a significant difference between the means of SCCF1 cells that received 0 Gy and 9 Gy (p=0.019), as well as 3 Gy and 9 Gy (p=0.022) when assessing the DNA in the tail. The difference between the means for comet tail moment was significant for SCCF1 at 0 Gy and 9 Gy, which corroborates part of the previous finding. Based on other experiments that evaluated clonogenic and comet assays together, correlation between the greatest mean tail moment and lowest surviving fraction indicate radiosensitivity, not cytotoxicity. The clinical feasibility of performing the comet assay on FOSCC tumor biopsies to elucidate radioresponsiveness prior to initiating treatment remains questionable for this specific disease. Performing the comet assay to evaluate DNA repair capabilities is recommended at various time intervals after irradiation to optimize fractionation protocols. Validation of DNA damage from double-stranded breaks could be compared using a chemiluminescent assay to detect levels of mouse anti-human monoclonal antibody for γ-H2AX.
Degree
M.S.