Intercellular distribution of aberrations detected by means of chromosome painting in cells of patients with cancer prone chromosome instability syndromes

A three-color chromosome in situ suppression (CISS) hybridization technique (chromosome painting) was applied to analyze spontaneous and induced (by i n vitro irradiation) chromosomal aberrations in peripheral lymphocytes and lymphoblastoid cell lines of homozygote and heterozygote individuals with a taxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS). The paintin g technique employing for hybridization DNA libraries of the chromosomes 1, 2, and 4 allows the additional detection of chromosomal rearrangements whi ch are not or at least not easily detectable by the classical cytogenetic m ethods. In all investigated groups the observed intercellular distribution of chrom osomal aberrations and breaks was compared with Poisson distribution and ge ometric distribution. In the lymphocytes of homozygous patients with AT a v ery high level of chromosomal aberrations and breaks was induced by the irr adiation of cultures at a dose of 2.0 Gy, as compared with AT heterozygotes irradiated with the same dose. The observed distributions of chromosomal a berrations in cells fitted Poisson distribution in the absolute majority of variants, while geometric distribution fitted much lesser number of varian ts. In AT heterozygotes individuals levels of chromosomal aberrations induc ed by in vitro irradiation at a dose of 2.0 Gy were lower than in AT homozy gotes, and their observed distributions were mainly described by geometric distribution and only in a few cases by Poisson distribution. In one NBS ho mozygous patient the comparatively low level of aberrations per cell upon i rradiation at a dose of 2.0 Gy was described by geometric distribution, whi le under identical experimental conditions, in the group of NBS heterozygou s individuals the low levels of chromosomal aberrations per cell were descr ibed both by Poisson and geometric distribution. The low levels of spontane ous and radiation-induced chromosomal aberrations in all investigated group s fitted both distributions. The distributions of breaks in the absolute ma jority of irradiated variants fitted neither Poisson nor geometric distribu tion requiring further comparison with other distributions or combination o f distributions. The problems of description of observed distributions by t he theoretical ones are discussed taking into account specific experimental conditions or nonspecific parameters, Comparative analysis of intercellula r distributions could be regarded as an informative cytogenetic approach to the research of radiosensitivity in the patients with chromosomal instabil ity.