Delayed chromosomal instability induced by DNA damage.

Marder, B.; Morgan, William F.

doi:10.1128/mcb.13.11.6667

Cited by 221 publications

(96 citation statements)

References 39 publications

(62 reference statements)

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“…The chromosome instability seen in these GM10115 cells manifests itself as increases in dicentric chromosomes and translocations (Marder and Morgan, 1993;Kaplan et al, 1997;Limoli et al, 1997). These alterations imply high spontaneous rates of chromosome breakage and recombination.…”

Section: Discussionmentioning

confidence: 99%

A role for chromosomal instability in the development of and selection for radioresistant cell variants

et al. 2001

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Summary Chromosome instability is a common occurrence in tumour cells. We examined the hypothesis that the elevated rate of mutation formation in unstable cells can lead to the development of clones of cells that are resistant to the cancer therapy. To test this hypothesis, we compared chromosome instability to radiation sensitivity in 30 independently isolated clones of GM10115 human-hamster hybrid cells. There was a broader distribution of radiosensitivity and a higher mean SF 2 in chromosomally unstable clones. Cytogenetic and DNA double-strand break rejoining assays suggest that sensitivity was a function of DNA repair efficiency. In the unstable population, the more radioresistant clones also had significantly lower plating efficiencies. These observations suggest that chromosome instability in GM10115 cells can lead to the development of cell variants that are more resistant to radiation. In addition, these results suggest that the process of chromosome breakage and recombination that accompanies chromosome instability might provide some selective pressure for more radioresistant variants.

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Section: Discussionmentioning

confidence: 99%

A role for chromosomal instability in the development of and selection for radioresistant cell variants

et al. 2001

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“…Chromosomes were counterstained with propidium iodide (C and E) or 4Ј, 6-diamidino-2-phenylindole (D and F). Another well-documented example of genetic instability found in mammalian cells occurs at a delayed time after exposure to ionizing radiation (16,17). This delayed or persistent chromosomal instability can occur in vitro or in vivo and is characterized by the appearance of new chromosome translocations and rearrangements for many generations after an initial exposure to ionizing radiation (18,19).…”

Section: Discussionmentioning

confidence: 99%

Ionizing Radiation Induces Frequent Translocations with Delayed Replication and Condensation

Breger¹,

Smith²,

Turker

et al. 2004

Cancer Research

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Certain chromosome rearrangements display a significant delay in replication timing that is associated with a delay in mitotic chromosome condensation. Chromosomes with delay in replication timing/delay in mitotic chromosome condensation participate in frequent secondary rearrangements, indicating that cells with delay in replication timing/delay in mitotic chromosome condensation display chromosomal instability. In this report, we show that exposing cell lines or primary blood lymphocytes to ionizing radiation results in chromosomes with the delay in replication timing/delay in mitotic chromosome condensation phenotype, and that the delay in replication timing/delay in mitotic chromosome condensation phenotype occurs predominantly on chromosome translocations. In addition, exposing mice to ionizing radiation also induces cells with delay in replication timing/delay in mitotic chromosome condensation chromosomes that persist for as long as 2 years. Cells containing delay in replication timing/delay in mitotic chromosome condensation chromosomes frequently display hyperdiploid karyotypes, indicating that delay in replication timing/delay in mitotic chromosome condensation is associated with aneuploidy. Finally, using a chromosome engineering strategy, we show that only a subset of chromosome translocations displays delay in replication timing/delay in mitotic chromosome condensation. Our results indicate that specific chromosome rearrangements result in the generation of the delay in replication timing/delay in mitotic chromosome condensation phenotype and that this phenotype occurs frequently in cells exposed to ionizing radiation both in vitro and in vivo.

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“…Genomic instability may also be induced in a fraction of clones surviving radiation exposure (reviewed in Morgan et al, 1996;Little, 2000;Morgan, 2003); some of the first descriptions of the manifestations of radiation-induced genomic instability were delayed, nonclonal chromosomal aberrations (Pampfer and Streffer, 1989;Kadhim et al, 1992;Sabatier et al, 1992;Holmberg et al, 1993;Marder and Morgan, 1993;Grosovsky et al, 1996), increased mutation rates (Chang and Little, 1992;Harper et al, 1997), delayed reproductive cell death (Gorgojo and Little, 1989), and lethal mutations (Seymour et al, 1986). These continue to be the most extensively studied end points of radiation-induced genomic instability (Morgan, 2003).…”

Section: Introductionmentioning

confidence: 99%

Role of genetic background in induced instability

Kadhim

2003

Oncogene

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Genomic instability is effectively induced by ionizing radiation. Recently, evidence has accumulated supporting a relationship between genetic background and the radiation-induced genomic instability phenotype. This is possibly due to alterations in proteins responsible for maintenance of genomic integrity or altered oxidative metabolism. Studies in human cell lines, human primary cells, and mouse models have been performed predominantly using high linear energy transfer (LET) radiation, or high doses of low LET radiation. The interplay between genetics, radiation response, and genomic instability has not been fully determined at low doses of low LET radiation. However, recent studies using low doses of low LET radiation suggest that the relationship between genetic background and radiation-induced genomic instability may be more complicated than these same relationships at high LET or high doses of low LET radiation. The complexity of this relationship at low doses of low LET radiation suggests that more of the population may be at risk than previously recognized and may have implications for radiation risk assessment.

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Delayed chromosomal instability induced by DNA damage.

Cited by 221 publications

References 39 publications

A role for chromosomal instability in the development of and selection for radioresistant cell variants

A role for chromosomal instability in the development of and selection for radioresistant cell variants

Ionizing Radiation Induces Frequent Translocations with Delayed Replication and Condensation

Role of genetic background in induced instability

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