LETHALITY OF RADIATION-INDUCED CHROMOSOME-ABERRATIONS IN HUMAN TUMOR-CELL LINES WITH DIFFERENT RADIOSENSITIVITIES

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 t ypes, three-colour fluorescence in situ hybridization was performed, i ncluding a whole-chromosome probe, a pancentromere probe, and a stain for total DNA. This technique enables the appropriate classification o f the aberrations principally by the presence (stable) or not (unstabl e) of a single centromere per chromosome. Unstable-type aberrations we re found to disappear within 7 days (several divisions) in the two rad iosensitive and the two radioresistant tumour lines investigated. Stab le-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 stab le-type aberrations had disappeared by 14 days in the two radiosensiti ve lines. The previous findings of disappearance of total aberrations in radiosensitive cells was therefore not due to a reduced induction o f stable-type aberrations, but the complete disappearance of cells wit h this aberration type. These results could not be explained by differ ences in apoptosis or G(1) blocks. Two possible explanations for these unexpected findings involve non-random induction of unstable-type abe rrations, or lethality of stable-type aberrations. The results suggest caution in the use of stable-type aberration numbers as a predictor f or radiosensitivity.