title: Micronuclei and apoptosis in glioma and neuroblastoma cell lines and role of other lesions in the reconstruction of cellular radiosensitivity.
abstract: It is now well established that micronuclei frequency does not always rank cell lines according to radiosensitivity. There is, however, a growing interest in reconstructing cellular radiosensitivity (measured by colony assay) from concurrent micronucleus and apoptosis data. Using a variety of radiosensitive and radioresistant cell lines, we have derived a missing parameter--Poe, the probability of cell death by other events such as small deletions, chromosome aberrations, late apoptosis and necrosis which are undetectable by micronucleus and apoptosis assays performed at a single time point. In the radioresistant glioma cell lines G120, G60, G28, G44 and G62 (SF2 > or =0.59), a characteristic threshold dose exists above which cell loss due to undetectable lesions occurs. In the radiosensitive SK-N-SH and KELLY cell lines (SF2 < or =0.43), the Poe parameter is positive at very low doses, reaches a maximum and declines at higher doses. In the radiation resistant G28 cells, Poe was found to be below zero for doses up to 6 Gy. In the G62, G44 and G120 cell lines, the threshold doses to induce Poe events were 0.87, 3.04 and 3.85 Gy, respectively. Cell death by undetectable lesions is a cell-specific and time-dependent variable. Micronucleus and apoptosis assays performed concurrently and at a specific time point miss cell death due to other events and this may be the reason why reconstruction of cellular radiosensitivity from micronucleus and apoptosis data fails.
authors.affiliation: Department of Radiation Oncology, Faculty of Medical Sciences and Tygerberg Hospital, University of Stellenbosch, South Africa.
authors.forename: J M
authors.initials: JM
authors.lastname: Akudugu
authors.forename: L
authors.initials: L
authors.lastname: Böhm
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D048629:Micronuclei, Chromosome-Defective / Q000378:metabolism*; D015162:Micronucleus Tests / Q000379:methods; D009447:Neuroblastoma / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured