Radiation-induced comet-formation in human skin fibroblasts from radiotherapy patients with different normal tissue reactions

Background: In clinical radiotherapy most patients tolerate the applied dos age with no or moderate side effects. However, 5 to 10% of all individuals show increased acute and/or late reactions. In-vitro test systems are inves tigated for their suitability for predictive purposes. This paper attempts a correlation between the induction and repair of DNA damage measured in th e comet assay and the clinical observed reaction in order to evaluate the s uitability of the comet assay for prediction of radiation sensitivity. Patients and Methods: Skin fibroblasts of 30 patients with avt rage tissue reactions or acute and/or late increased side effects and cell lines of 4 i ndividuals carrying the heritable disease ataxia telangiectasia (AT) were i rradiated in vitro. The induction and repair of DNA damage was measured at different time points after irradiation in the comet assay (single cell gel electrophoresis). These results were compared to the acute and late clinic al reactions classified according to the RTOG grading system. Results: The radiation induced DNA damage decreased over time reflecting DN A repair. Cells of the AT individuals showed an elevated damage induction a nd a reduced repair capacity compared to patients with average tissue react ions. Fibroblasts of patients with increased acute and late side effects ex hibited slower DNA repair. In addition to the known lack of cell cycle cont rol, our results indicate that AT cells show reduced DNA repair capacity. Conclusions: The comet assay seems to be able to detect some types of incre ased individual radiation sensitivity. In contrast to other predictive in-v itro tests. the comet assay needs less time and fewer cells, which would be useful in a clinical selling.