Cell-age heterogeneity and deviations from the LQ model in the radiation survival responses of human tumour cells

Abstract

Purpose: To determine whether some of the deviations from the simple linear-quadratic (LQ) theory in the radiation dose-survival responses of asynchronous cultures of human tumour cell lines are caused by the presence of cell-agespecific subpopulations which all individually follow LQ theory, but have different radiosensitivities. Materials and methods: Human tumour cells were synchronized by mitotic selection and their survival dose responses were measured at doses from 0.05Gy to 12Gy, using a high-precision survival assay. These responses were compared with a kinetic model of radiation survival in synchronized cells, which assumed that age-specific populations individually obeyed the LQ theory. The cell lines used included HT-29 and A549, which have typical dose responses, and U1, which is somewhat atypical. Results: In two of the three cell lines, A549 and HT-29, observed deviations from the LQ model were consistent with those expected from cell-age heterogeneity. In the third cell line, U1, survival responses could not be described by the LQ theory, even when cell-age heterogeneity was considered. Conclusions: The LQ model provided an adequate description of cell survival for two of three tumour cell lines in this study when cell-age related heterogeneity in survival responses was accounted for. However, some alternative survival models (such as the repair saturation model) provided better characterizations of the survival response of the third cell line and, in fact, gave good descriptions of survival for all three cell lines.