Radiation-induced genomic instability in repair deficient mutants of Chinese hamster cells

Somodi, Zsolt; Zyuzikov, Nikolay A.; Kashino, Genro; Trott, K.R.; Prise, Kevin M.

doi:10.1080/09553000600570446

Cited by 13 publications

(8 citation statements)

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“…In the present study, we confirmed the induction of delayed genetic effects especially at low X-ray doses. As shown in our previous report (Somodi et al 2005), cells that are defective in single strand breaks repair are susceptible to radiation induced delayed effects at high doses. Our present study also shows higher delayed induction of micronuclei in EM9, suggesting that unrepaired or misrepaired DNA damageare important for the expression of delayed genetic effects at low X-ray doses.…”

Section: Discussionsupporting

confidence: 64%

“…Radiation induced genomic instability has been reported by many groups (Kadhim et al 1992;Little et al 1997;Morgan. 2003ab;Suzuki et al 2003Suzuki et al , 2009Suzuki et al , 2010Somodi et al 2005;Seoane et al 2007;Toyokuni et al 2009). This form of damage is apparent in growing cells several generations after irradiation of the initial cell population.…”

Section: Introductionmentioning

confidence: 99%

“…In these investigations, repair deficient cell lines derived from Chinese hamster ovary (CHO) cells have been used as described in previous reports (Thacker and Zdzienicka 2003;Kashino et al 2004;Somodi et al 2005). In the present study, we investigated the X-ray induced delayed effects in repair deficient CHO cell lines to elucidate the mechanisms of genomic instability induced by lower doses of X-irradiation.…”

Section: Introductionmentioning

confidence: 99%

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Increased susceptibility to delayed genetic effects of low dose X-irradiation in DNA repair deficient cells

Kashino

Suzuki

Kodama

et al. 2012

International Journal of Radiation Biology

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased susceptibility to delayed genetic effects of low dose X-irradiation in DNA repair deficient cells

Kashino

Suzuki

Kodama

et al. 2012

International Journal of Radiation Biology

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“…Clustered DNA damages are hypothesized to be poorly repaired lesions that produce cytotoxic and mutagenic effects (14-16) as well as chromosomal instability (17). Although multiple pathways for the induction and perpetuation of genomic instability are possible (18), studies conducted with repair-deficient cells lines suggest that DSBs and other forms of complex damage are involved in genomic instability (19)(20)(21).…”

Section: Introductionmentioning

confidence: 98%

Induction and Processing of Oxidative Clustered DNA Lesions in⁵⁶Fe-Ion-Irradiated Human Monocytes

et al. 2007

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Space and cosmic radiation is characterized by energetic heavy ions of high linear energy transfer (LET). Although both low- and high-LET radiations can create oxidative clustered DNA lesions and double-strand breaks (DSBs), the local complexity of oxidative clustered DNA lesions tends to increase with increasing LET. We irradiated 28SC human monocytes with doses from 0-10 Gy of (56)Fe ions (1.046 GeV/ nucleon, LET = 148 keV/microm) and determined the induction and processing of prompt DSBs and oxidative clustered DNA lesions using pulsed-field gel electrophoresis (PFGE) and Number Average Length Analysis (NALA). The (56)Fe ions produced decreased yields of DSBs (10.9 DSB Gy(-1) Gbp(-1)) and clusters (1 DSB: approximately 0.8 Fpg clusters: approximately 0.7 Endo III clusters: approximately 0.5 Endo IV clusters) compared to previous results with (137)Cs gamma rays. The difference in the relative biological effectiveness (RBE) of the measured and predicted DSB yields may be due to the formation of spatially correlated DSBs (regionally multiply damaged sites) which result in small DNA fragments that are difficult to detect with the PFGE assay. The processing data suggest enhanced difficulty compared with gamma rays in the processing of DSBs but not clusters. At the same time, apoptosis is increased compared to that seen with gamma rays. The enhanced levels of apoptosis observed after exposure to (56)Fe ions may be due to the elimination of cells carrying high levels of persistent DNA clusters that are removed only by cell death and/or "splitting" during DNA replication.

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“…Although our analysis of UV-induced DHR focused on a single cell type derived from a human tumor, it is likely to be a general effect because the various forms of delayed genomic instability have been observed in a wide variety of cell types, in animal models, and after exposures to many types of genotoxic agents (13,16,22,24,30,52,60,64). In addition, the RKOderived cells we studied express functional p53 (33), so DHR is not restricted to p53-defective cells (i.e., the majority of tumor cells).…”

Section: Discussionmentioning

confidence: 99%

UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells

Durant

Paffett

Shrivastav

et al. 2006

Molecular and Cellular Biology

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Ionizing radiation induces delayed genomic instability in human cells, including chromosomal abnormalities and hyperrecombination. Here, we investigate delayed genome instability of cells exposed to UV radiation. We examined homologous recombination-mediated reactivation of a green fluorescent protein (GFP) gene in p53-proficient human cells. We observed an ϳ5-fold enhancement of delayed hyperrecombination (DHR) among cells surviving a low dose of UV-C (5 J/m 2 ), revealed as mixed GFP ؉/؊ colonies. UV-B did not induce DHR at an equitoxic (75 J/m 2 ) dose or a higher dose (150 J/m 2 ). UV is known to induce delayed hypermutation associated with increased oxidative stress. We found that hypoxanthine phosphoribosyltransferase (HPRT) mutation frequencies were ϳ5-fold higher in strains derived from GFP ؉/؊ (DHR) colonies than in strains in which recombination was directly induced by UV (GFP ؉ colonies). To determine whether hypermutation was directly caused by hyperrecombination, we analyzed hprt mutation spectra. Large-scale alterations reflecting large deletions and insertions were observed in 25% of GFP ؉ strains, and most mutants had a single change in HPRT. In striking contrast, all mutations arising in the hypermutable GFP ؉/؊ strains were small (1-to 2-base) changes, including substitutions, deletions, and insertions (reminiscent of mutagenesis from oxidative damage), and the majority were compound, with an average of four hprt mutations per mutant. The absence of large hprt deletions in DHR strains indicates that DHR does not cause hypermutation. We propose that UV-induced DHR and hypermutation result from a common source, namely, increased oxidative stress. These two forms of delayed genome instability may collaborate in skin cancer initiation and progression.UV radiation elicits many cellular stress responses attributed to its induction of reactive oxygen species (ROS) and its ability to directly damage DNA, predominantly forming cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone 6-4 photoproducts (12,38,68). UV also indirectly produces single-strand breaks and double-strand breaks (DSBs) during DNA replication (42). Because UV can produce strand breaks and other DNA lesions in several ways, it is a powerful mutagen and carcinogen. Solar UV-A (320 to 400 nm) and the higher-energy and shorter wavelength UV-B (290 to 320 nm) penetrate the Earth's atmosphere, and chronic exposures have been linked to melanoma, the most fatal form of skin cancer (56). UV-C (100 to 290 nm) has the highest energy but is blocked by the ozone layer. However, UV-C exposures are possible from artificial sources, including germicidal lamps, arc welding equipment, and mercury arc lamps in older tanning beds. A significant fraction of UV damage is repaired by the nucleotide excision repair system, and patients with nucleotide excision repair defects show marked susceptibility to skin cancer (1, 27, 56). Human nonmelanoma skin cancer correlates with sun exposure (1) and is often associated with p53 mutations at dipyrimidines...

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Radiation-induced genomic instability in repair deficient mutants of Chinese hamster cells

Abstract: SSB and/or oxidized base damage play a major role, rather than DSB, in radiation induced instability.

Cited by 13 publications

References 43 publications

Increased susceptibility to delayed genetic effects of low dose X-irradiation in DNA repair deficient cells

Increased susceptibility to delayed genetic effects of low dose X-irradiation in DNA repair deficient cells

Induction and Processing of Oxidative Clustered DNA Lesions in⁵⁶Fe-Ion-Irradiated Human Monocytes

UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells

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Radiation-induced genomic instability in repair deficient mutants of Chinese hamster cells

Abstract: SSB and/or oxidized base damage play a major role, rather than DSB, in radiation induced instability.

Cited by 13 publications

References 43 publications

Increased susceptibility to delayed genetic effects of low dose X-irradiation in DNA repair deficient cells

Increased susceptibility to delayed genetic effects of low dose X-irradiation in DNA repair deficient cells

Induction and Processing of Oxidative Clustered DNA Lesions in56Fe-Ion-Irradiated Human Monocytes

UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells

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Induction and Processing of Oxidative Clustered DNA Lesions in⁵⁶Fe-Ion-Irradiated Human Monocytes