Cell cycle dependent aneuploidy induction by X-rays in vitro in human lymphocytes

Although ionising radiation mainly induces DNA strand breaks leading to chromosomal aberrations, there are indications that it also might induce numerical chromosome aberrations (aneuploidy). The existing data, however, do not provide evidence for a mechanism. To assess the relative sensitivity of the G1 vs. G2 cellular targets, whole blood cultures of lymphocytes were irradiated in vitro with different doses of X-rays (0.5, 1 and 2 Gy). The lymphocytes were harvested after cytochalasin-B blockade to allow the selective study of binucleated cells, having undergone only one division in culture. Harvesting was performed at different sampling times (70, 74, and 78 hours). To evaluate the micronuclei, regarding whole chromosomes or acentric fragments, an oligonucleotide probe that recognises the centromeric region of all human chromosomes was used. The relative percentage of centromere-positive micronuclei ranged from 5 up to 18% depending on the cell cycle stage and on the received dose. Cells exposed during the G1 phase exhibited a slightly higher frequency of centromere-positive micronuclei than cells that were in G2 at the time of exposure. G1 exposure induced a centromere-positive micronuclei dose-effect relationship that was not observed after G2 exposure. The observed difference in response of both phases on the centromere-positive micronuclei yields may be due to the involvement of different targets.