A unifying model for reconstructing radiosensitivity from micronucleus formation, apoptosis and abnormal morphology

At present micronucleus data cannot predict cellular radiosensitivity. The inclusion of data from apoptosis and abnormal morphology has not entirely resolved this problem. Here, we assess the probability of cell death arising from events other than micronucleation, apoptosis and abnormal morphology (i.e. lesions not detected by these damage assays) P _oe, for its ability to reflect intrinsic cellular radiosensitivity. Analysis of data from 17 cell lines used in two separate studies, spanning a wide range of radiosensitivity (0.09≤SF2≤0.70), confirmed our previous observation that cell death due to undetected lesions depends on the irradiation dose and is cell type-specific. We further demonstrate that P _oe accounts for inter-cell line differences in translating irradiation damage into cell death. Data from any two of micronucleus formation, apoptosis and abnormal cell morphology, fitted to the P _oe model, adequately predict clonogenic survival, and measurement of additional damage endpoints is not required. The P _oe model may benefit patient selection in situations where colony formation of primary tumour cultures fails to arrive at estimates of radiosensitivity.