title: Lethality of radiation-induced chromosome aberrations in human tumour cell lines with different radiosensitivities.
abstract: In order to find an explanation for the eventual disappearance of all chromosome aberrations in two radiosensitive human tumour cell lines, the type and stability of different aberration types was investigated in more detail. To classify the aberrations into unstable and stable types, three-colour fluorescence in situ hybridization was performed, including a whole-chromosome probe, a pancentromere probe, and a stain for total DNA. This technique enables the appropriate classification of the aberrations principally by the presence (stable) or not (unstable) of a single centromere per chromosome. Unstable-type aberrations were found to disappear within 7 days (several divisions) in the two radiosensitive and the two radioresistant tumour lines investigated. Stable-type aberrations were found to remain at an approximately constant level over the duration of the experiment (14 days; 8-10 divisions) in the two radioresistant lines. In contrast, the majority of these stable-type aberrations had disappeared by 14 days in the two radiosensitive lines. The previous findings of disappearance of total aberrations in radiosensitive cells was therefore not due to a reduced induction of stable-type aberrations, but the complete disappearance of cells with this aberration type. These results could not be explained by differences in apoptosis or G1 blocks. Two possible explanations for these unexpected findings involve non-random induction of unstable-type aberrations, or lethality of stable-type aberrations. The results suggest caution in the use of stable-type aberration numbers as a predictor for radiosensitivity.
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Coco-Martin
authors.forename: C P
authors.initials: CP
authors.lastname: Ottenheim
authors.forename: H
authors.initials: H
authors.lastname: Bartelink
authors.forename: A C
authors.initials: AC
authors.lastname: Begg
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011836:Radiation Tolerance / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000528:radiation effects* / Q000648:ultrastructure