INTERCELLULAR DISTRIBUTION OF ABERRATIONS DETECTED BY MEANS OF CHROMOSOME PAINTING IN CELLS OF PATIENTS WITH CANCER PRONE CHROMOSOME INSTABILITY SYNDROMES

Arutyunyan R., Neubauer S., Martus P., Dork T., Stumm M., Gebhart E.

A three-color chromosome in situ suppression (CISS) hybridization technique (chromosome painting) was applied to analyze spontaneous and induced (by in vitro irradiation) chromosomal aberrations in peripheral lymphocytes and lymphoblastoid cell lines of homozygote and heterozygote individuals with ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS). The painting technique employing for hybridization DNA libraries of the chromosomes 1, 2, and 4 allows the additional detection of chromosomal rearrangements which are not or at least not easily detectable by the classical cytogenetic methods.
In all investigated groups the observed intercellular distribution of chromosomal aberrations and breaks was compared with Poisson distribution and geometric distribution. In the lymphocytes of homozygous patients with AT a very high level of chromosomal aberrations and breaks was induced by the irradiation of cultures at a dose of 2.0 Gy, as compared with AT heterozygotes irradiated with the same dose. The observed distributions of chromosomal aberrations in cells fitted Poisson distribution in the absolute majority of variants, while geometric distribution fitted much lesser number of variants. In AT heterozygous individuals levels of chromosomal aberrations induced by in vitro irradiation at a dose of 2.0 Gy were lower than in AT homozygotes, and their observed distributions were mainly described by geometric distribution and only in a few cases by Poisson distribution. In one NBS homozygous patient the comparatively low level of aberrations per cell upon irradiation at a dose of 2.0 Gy was described by geometric distribution, while under identical experimental conditions, in the group of NBS heterozygous individuals the low levels of chromosomal aberrations per cell were described both by Poisson and geometric distribution. The low levels of spontaneous and radiation-induced chromosomal aberrations in all investigated groups fitted both distributions. The distributions of breaks in the absolute majority of irradiated variants fitted neither Poisson nor geometric distribution reguiring further comparison with other distributions or combination of distributions. The problems of description of observed distributions by the theoretical ones are discussed taking into account specific experimental conditions or nonspecific parameters. Comparative analysis of intercellular distributions could be regarded as an informative cytogenetic approach to the research of radiosensitivity in the patients with chromosomal instability.

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