Analysis of chromosome loss and non-disjunction in cytokinesis-blocked lymphocytes of 24 male subjects

Chromosome malsegregation in peripheral blood lymphocytes of 24 healthy mal e subjects was analysed by means of fluorescence in situ hybridization with centromeric probes of chromosomes 7, 11, 18 and X. On the basis of the dis tribution of centromeric signals in cytokinesis-blocked cells, both loss (l eading to centromere-positive micronuclei) and non-disjunction (resulting i n an unbalanced distribution of signals in the main nuclei) of the hybridiz ed chromosomes in vitro were identified. In addition, the incidence of binu cleated cells with two hyperploid nuclei, possibly arising from mitotic div ision of trisomic types, was determined. In this way, the incidence of chro mosome malsegregation in vivo and in vitro could be compared in the same ce ll samples. The results obtained show that ageing is positively correlated with the incidence of malsegregation of chromosome X in peripheral lymphocy tes of male subjects and confirm the higher susceptibility of chromosome X to malsegregation in comparison with autosomes, A positive correlation betw een in vitro and in vivo malsegregation rates was observed for both chromos ome X and for autosomes, Finally, relatively high frequencies of multiple m alsegregation events, greater than expected for independent events, were re corded for both chromosome X and for autosomes, indicating that the abnorma l segregation of chromosomes may be connected to a general dysfunction of t he mitotic apparatus. The correlation observed between in vitro and in vivo malsegregation frequencies and the association of both parameters with age ing suggest that analysis of chromosome malsegregation in binucleated cells is a useful tool in the study of genomic instability in human populations.