Equal induction and persistence of chromosome aberrations involving chromosomes with heterogeneous lengths and gene densities

Abstract

Little is known about the factors modulating the initial induction and persistence of chromosome aberrations. Chromosome length and gene density have been proposed to play a significant role. We have therefore analyzed the induction and persistence of γ-ray-induced aberrations involving four human chromosomes (1, 4, 18, and 19) with highly heterogeneous lengths and gene densities. Multicolor FISH was performed on a wild-type lymphoblastoid cell line 1, 3, 7, 14, 28, 42, and 56 d after γ-irradiation. The frequency of induced chromosomal aberrations was proportional to the length of the chromosomes. Complex aberrations, dicentrics, and fragments were highly unstable and disappeared during the first week after treatment and with similar kinetics for all four chromosomes. The frequency of translocations decreased with time and followed an exponential decline. Thirty percent of the γ-ray-induced translocations were stable over the entire study period, irrespective of the length and the gene density of the chromosome involved. Accordingly, we concluded that the induction of chromosome aberrations is proportional to the length of the chromosome, that gene density makes no measurable contribution to induction, and that neither length nor gene density influences the persistence of chromosome aberrations.

Quantitative relationships for radiation induced chromosome instability: data analysis

“…Fig. 3 shows the experimental data on the dynamics of RICI for the other two cell lines, V79 [2] and TK6 [3], together with their quantitative description by the theoretical model. It should be mentioned that the experimental data on TK6 cells [3] have been published dimensionless using FISH painting of four chromosomes.…”

“…3 shows the experimental data on the dynamics of RICI for the other two cell lines, V79 [2] and TK6 [3], together with their quantitative description by the theoretical model. It should be mentioned that the experimental data on TK6 cells [3] have been published dimensionless using FISH painting of four chromosomes. For comparability we merged and normalized the data so that the first point (t = 1 day) was close to the point corresponding to a dose of 3 Gy and a time of 30 hours in [4].…”

“…We have developed a computer model of radiation-induced chromosomal instability (RICI) [1]. This paper is devoted the analysis of the results of own experiments together with the published data [2,3]. The findings and experimental procedure are presented in the following sections.…”

Comparative analysis of individual chromosome involvement in micronuclei induced by mitomycin C and bleomycin in human leukocytes

“…Chromosomes can be thought to be incorporated into MN depending on their size and/or gene density [ 13 ], as well as the general nuclear chromatin organization [ 14 , 15 ], and/or lethality of chromosomal (partial) loss for the cells [ 9 ]. However, despite existing information the data on involvement of various types of chromosomes and chromosomal fragments in mutagens-induced MN is still limited, even though further characterization of MN contents is crucial for understanding and accurate application of the MN assay.…”

Fluorescence in situ hybridization is necessary to detect an association between chromosome aberrations and polycyclic aromatic hydrocarbon exposure in utero and reveals nonrandom chromosome involvement

“…It was based on the theory that the probability of an aberrant event occurring in any particular chromosome is determined by its DNA content [Lucas et al, 1992;Tucker et al, 1993]. This theory has been substantiated in some radiation and chromosome aberration studies that have demonstrated a linear relationship between DNA content and breakpoints, i.e., larger chromosomes are subject to more breaks [Puerto et al, 1999b;Johnson et al, 1999;Sachs et al, 2000]. However, multiple studies have demonstrated that chromosome aberrations induced with radiation and chemicals are not randomly distributed by chromosome size [Knehr et al, 1996;Stephan and Pressl, 1997;Barquinero et al, 1998;Smith et al, 1998;Wu et al, 1998;Zhang et al, 1998aZhang et al, ,b, 2005Eastmond et al, 2001;Verdorfer et al, 2001;Zhu et al, 2002;Beskid et al, 2006].…”