Analysis of chromosome loss and chromosome segregation in cytokinesis-blocked human lymphocytes: Non-disjunction is the prevalent mistake in chromosome segregation produced by low dose exposure to ionizing radiation

Abstract

The aim of the present work was to examine in human lymphocytes, firstly, whether in vitro γ-rays as compared with X-rays also induce chromatid malsegregation and at higher frequencies than chromosome loss and, secondly, whether the cytokinesis-blocked micronucleus assay combined with fluorescence in situ hybridization might be useful for the biomonitoring of individuals exposed to ionizing radiation. After irradiation, the relative frequencies of centromere-positive micronuclei decreased from 39.2 at 0.1 Gy to 21.63 at higher doses. There was no statistically significant increase in MNCen + frequencies at doses below 1 Gy (0.1, 0.25 and 0.5 Gy), but a statistically significant increase at 1 (P < 0.05) and 2 Gy (P < 0.001) was observed for all the donors. No significant differences in baseline and γ-ray-induced non-disjunction frequencies for chromosomes 1 (P = 0.9) and 17 (P = 0.8) between individuals were detected. For radiation-induced non-disjunction, lower doses (0.1, 0.25 and 0.5 Gy) of γ-rays did not induce a statistically significant increase in nondisjunction frequencies whereas 1 Gy and above clearly induced a statistically significant increase in the total nondisjunction frequencies for all the donors (P < 0.05 at 1 Gy and P < 0.0001 at 2 Gy). The aneugenic effect of radiation is less clearly dose dependent at the lower doses, suggesting an apparent threshold below which no change could be demonstrated. At high radiation doses the major mechanism for γ-ray-induced aneuploidy is related to chromosome loss through non-disjunction, as has been demonstrated using X-rays, and not through the formation of micronuclei.