An Evaluation of the Frequency of Spontaneous Aneuploidy in Human Somatic Cells Using the Technology of Interphase Cytogenetics

Abstract

The frequency of spontaneous aneuploidy of the four autosomes and both sex chromosomes in the interphase nuclei of cultured and noncultured lymphocytes from clinically healthy men was examined by use of two-color fluorescent in situ hybridization (FISH). It was shown that in noncultured cells from the individuals examined autosomal nullisomies were practically not detected (the frequency 0 to 0.01%). At the same time, the frequency of such cells with either Y, or X nullisomy was at least an order of magnitude higher (about 0.15%). This frequency was comparable with the level of Y- or X-disomic cells, and also with autosomal monosomies, precluding from consideration of X-nullisomic cells as hybridization artifact. During lymphocyte cultivation, a statistically significant increase in the total frequency of Y- or X-nullisomic cells was observed already after the first cell division cycle. Thus, interphase FISH analysis is a sufficiently sensitive method enabling detection of higher, compared to the autosomes, loss of sex chromosomes in the process of cell division, a phenomenon observed during replicative cell aging, as well as during natural aging of the organism. Male cells with the de novo lost single X chromosome, probably, switch to apoptosis and do not survive during further life of a cell population. The frequency of total aneuploidy in human somatic cells with the correction for the resolution capacity of the interphase FISH analysis was estimated to be 5.62 and 6.90% for noncultured and cultured cells, respectively. This aneuploidy level is close to that in spermatozoa. The data obtained can serve as the basis for the examination of the aneugenic (aneuploidy-inducing) genotoxic effects and for the analysis of interindividual genetic instability.