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.
Akudugu
J M
JM
Department of Radiation Oncology, Faculty of Health Sciences and Tygerberg HospitalUniversity of Stellenbosch, P.O. Box 19063, 7505, Tygerberg, South Africa. jakudugu@uhnres.utoronto.ca
Abend
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M
Böhm
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D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000473:pathology; D015162:Micronucleus Tests / Q000379:methods*; D008962:Models, Theoretical; D011836:Radiation Tolerance; D013997:Time Factors