DELAYED CHROMOSOMAL INSTABILITY IN HUMAN T-LYMPHOCYTE CLONES EXPOSED TO IONIZING-RADIATION

Recent studies have demonstrated that cells which survive alpha-partic le and X-ray exposure may show chromosomal instability, i.e. they cont inue to develop chromosomal aberrations at an increased frequency for many division cycles after the exposure. To characterize this delayed response, we carried out repeated karyotype analyses of X-irradiated T -lymphocytes during clonal expansion in vitro. Human peripheral blood lymphocytes were obtained from a healthy donor and exposed to 3-Gy X-i rradiation. Cell survival, estimated by a cell cloning assay, was 5%. Non-irradiated, control cells were studied in parallel. Monoclonal cel l lines were established using the T-cell cloning procedure. G-band ka ryotype analyses were carried out at several intervals during expansio n of the clones for up to 2 months. The irradiated clones did not diff er from the control clones with regard to growth rate or cytometric DN A profile. Non-irradiated cell clones showed a normal karyotype, with < 10% of sporadic, non-clonal chromosome and chromatid breaks. In the irradiated clones, the karyotypes showed different subclonal chromosom e rearrangements, which developed successively during the cultivation time. In addition to these karyotypic abnormalities, > 20% of the cell s in these clones had sporadic, non-clonal chromosome aberrations, and there was a tendency of increasing frequency of such aberrations by l ength of cultivation. Thus, two types of radiation-induced chromosomal instability were observed; (sub)clonal karyotypic abnormalities and s poradic, non-clonal chromosome aberrations. The frequency and kinetics by which these alterations occur in the progeny of X-irradiated T-cel ls suggest that they arise through different pathways, and argue again st their causation by mutation or persistent DNA damage.