Evaluation of Capability and Relationship of Different Radiobiological Endpoints for Radiosensitivity Prediction in Human Tumor Cell Lines Compared with Clonogenic Survival

Abstract

Background: Establishing a predictive assay of radiosensitivity (as an appropriate, practical and cost-effective method) has been challenging. Objective: The purpose of this study is to evaluate the capability and relationship of various endpoints, including GammaH2AX, micronuclei; and apoptosis in determining the human tumor cell lines radiosensitivities compared with clonogenic survival.Material and Methods: In an experimental in-vitro study, the response of carcinoma cell lines of HN5 and HeLa to 2 Gy of 6 MV photon beam was investigated via various assays. Results: Survival fraction at 2 Gy (SF2) of HeLa and HN5 was indicated as 0.42 ± 0.06 and 0.5 ± 0.03 respectively, proposing more radioresistance of HN5. This finding was confirmed with “2 Gy apoptosis enhancement ratio” which was 1.77 and 1.42 in HeLa and HN5. The increased levels of DNA DSBs were observed after irradiation; significant in HeLa with enhancement rate of 19.24. The micronuclei formation followed an ascending trend post irradiation; but with the least difference between two cells. Although the relationship between micronuclei and clonogenic survival was moderate (R2 = 0.35), a good correlation was observed between apoptosis and clonogenic survival (R2 = 0.71). Conclusion: The results of studied endpoints agreed with the SF2, highlighting their capabilities in radiosensitivity prediction. In terms of the enhancement ratio, gammaH2AX foci scoring could be a valid indicator of radiosensitivity but not the exact surrogate marker of survival because no correlation was observed. Moreover, considering the chief determents comprising lack of time and money, the apoptotic induction might be an appropriate indicator with the best correlation coefficient.

Keywords

• radiosensitivity
• gammah2ax
• apoptosis
• dna damage
• radiobiology