DNA damage in cells exhibiting radiation-induced genomic instability

Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

doi:10.1093/mutage/gev006

Title: DNA damage in cells exhibiting radiation-induced genomic instability

Journal Article · Sun Feb 22 00:00:00 EST 2015 · Mutagenesis

DOI:https://doi.org/10.1093/mutage/gev006· OSTI ID:1214533

Keszenman, Deborah J. ^[1]; Kolodiuk, Lucia ^[2]; Baulch, Janet E. ^[3]

Brookhaven National Lab. (BNL), Upton, NY (United States). Biosciences Dept.; CENUR del Noroeste, Salto (Uruguay). Lab. of Medical and Environmental Radiobiology
Stony Brook Univ., Stony Brook, NY (United States)
Univ. of California, Irvine, CA (United States). Dept. of Radiation Oncology

Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesis that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Laboratory Directed Research and Development (LDRD) Program

Grant/Contract Number:: SC00112704

OSTI ID:: 1214533

Report Number(s):: BNL-108343-2015-JA; R&D Project: 12-012; YN0100000

Journal Information:: Mutagenesis, Vol. 30, Issue 3; ISSN 0267-8357

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 10 works

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References (51)

Expression of theE. coli fpg protein in CHO cells lowers endogenous oxypurine clustered damage levels and decreases accumulation of endogenousHprt mutations Paul, Sunirmal; Gros, Laurent; Laval, Jacques Environmental and Molecular Mutagenesis, Vol. 47, Issue 5 https://doi.org/10.1002/em.20208	journal	June 2006
The role of mitochondria in the oncogenic signal transduction Frezza, Christian The International Journal of Biochemistry & Cell Biology, Vol. 48 https://doi.org/10.1016/j.biocel.2013.12.013	journal	March 2014
Chromosomal instability induced by heavy ion irradiation L. Limoli, B. Ponnaiya, J. Corcoran, C. International Journal of Radiation Biology, Vol. 76, Issue 12 https://doi.org/10.1080/09553000050201082	journal	January 2000
Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation Sutherland, B. M.; Bennett, P. V.; Sidorkina, O. Proceedings of the National Academy of Sciences, Vol. 97, Issue 1 https://doi.org/10.1073/pnas.97.1.103	journal	January 2000
Clustered Damages and Total Lesions Induced in DNA by Ionizing Radiation: Oxidized Bases and Strand Breaks ^† Sutherland, Betsy M.; Bennett, Paula V.; Sidorkina, Olga Biochemistry, Vol. 39, Issue 27 https://doi.org/10.1021/bi9927989	journal	July 2000
DNA base repair – recognition and initiation of catalysis Dalhus, Bjørn; Laerdahl, Jon K.; Backe, Paul H. FEMS Microbiology Reviews, Vol. 33, Issue 6 https://doi.org/10.1111/j.1574-6976.2009.00188.x	journal	November 2009
Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated and Artemis for their repair Woodbine, Lisa; Brunton, H.; Goodarzi, A. A. Nucleic Acids Research, Vol. 39, Issue 16 https://doi.org/10.1093/nar/gkr331	journal	May 2011
A Role for Mitochondrial Dysfunction in Perpetuating Radiation-Induced Genomic Instability Kim, G. J.; Fiskum, G. M.; Morgan, W. F. Cancer Research, Vol. 66, Issue 21, p. 10377-10383 https://doi.org/10.1158/0008-5472.CAN-05-3036	journal	November 2006
Unrepaired clustered DNA lesions induce chromosome breakage in human cells Asaithamby, A.; Hu, B.; Chen, D. J. Proceedings of the National Academy of Sciences, Vol. 108, Issue 20 https://doi.org/10.1073/pnas.1016045108	journal	April 2011
Clustered DNA lesion repair in eukaryotes: Relevance to mutagenesis and cell survival Sage, Evelyne; Harrison, Lynn Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 711, Issue 1-2 https://doi.org/10.1016/j.mrfmmm.2010.12.010	journal	June 2011
Analysis of bleomycin-induced chromosomal aberrations in Chinese hamster primary embryonic cells by FISH using arm-specific painting probes Xiao, Y. Mutagenesis, Vol. 14, Issue 4 https://doi.org/10.1093/mutage/14.4.357	journal	July 1999
Biological consequences of formation and repair of complex DNA damage Magnander, Karin; Elmroth, Kecke Cancer Letters, Vol. 327, Issue 1-2 https://doi.org/10.1016/j.canlet.2012.02.013	journal	December 2012
Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer Sadikovic, B.; Al-Romaih, K.; Squire, J. Current Genomics, Vol. 9, Issue 6 https://doi.org/10.2174/138920208785699580	journal	September 2008
Hallmarks of Cancer: The Next Generation Hanahan, Douglas; Weinberg, Robert A. Cell, Vol. 144, Issue 5 https://doi.org/10.1016/j.cell.2011.02.013	journal	March 2011
Induction and Repair of Clustered DNA Lesions: What Do We Know So Far? Georgakilas, Alexandros G.; O'Neill, Peter; Stewart, Robert D. Radiation Research, Vol. 180, Issue 1 https://doi.org/10.1667/RR3041.1	journal	July 2013
Expression of delayed toxicity and lethal mutations in the progeny of human cells surviving exposure to radiation and other environmental mutagens Mothersill, C. International Journal of Radiation Biology, Vol. 74, Issue 6 https://doi.org/10.1080/095530098140934	journal	January 1998
Mitochondrial Dysfunction in Cancer Boland, Michelle L.; Chourasia, Aparajita H.; Macleod, Kay F. Frontiers in Oncology, Vol. 3 https://doi.org/10.3389/fonc.2013.00292	journal	January 2013
Mitochondrial Complex II Dysfunction Can Contribute Significantly to Genomic Instability after Exposure to Ionizing Radiation Dayal, Disha; Martin, Sean M.; Owens, Kjerstin M. Radiation Research, Vol. 172, Issue 6 https://doi.org/10.1667/RR1617.1	journal	December 2009
Delayed chromosomal instability induced by DNA damage. Marder, B. A.; Morgan, W. F. Molecular and Cellular Biology, Vol. 13, Issue 11, p. 6667-6677 https://doi.org/10.1128/MCB.13.11.6667	journal	November 1993
Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures Clutton, S. M.; Townsend, K. M. S.; Walker, C. Carcinogenesis, Vol. 17, Issue 8 https://doi.org/10.1093/carcin/17.8.1633	journal	January 1996
Melatonin protects human cells from clustered DNA damages, killing and acquisition of soft agar growth induced by X-rays or 970 MeV/n Fe ions Das, Birajalaxmi; Bennett, Paula V.; Cutter, Noelle C. International Journal of Radiation Biology, Vol. 87, Issue 6 https://doi.org/10.3109/09553002.2011.560993	journal	March 2011
Yields of Clustered DNA Damage Induced by Charged-Particle Radiations of Similar Kinetic Energy per Nucleon: LET Dependence in Different DNA Microenvironments Keszenman, Deborah J.; Sutherland, Betsy M. Radiation Research, Vol. 174, Issue 2 https://doi.org/10.1667/RR2093.1	journal	August 2010
Use of multicolour chromosome painting to identify chromosomal rearrangements in human lymphocytes exposed to bleomycin: A comparison with conventional cytogenetic analysis of giemsa-stained chromosomes Ellard, Sian; Parry, Elizabeth M.; Parry, James M. Environmental and Molecular Mutagenesis, Vol. 26, Issue 1 https://doi.org/10.1002/em.2850260107	journal	January 1995
Endogenous DNA damage clusters in human hematopoietic stem and progenitor cells Bennett, P.; Ishchenko, A.; Laval, J. Free Radical Biology and Medicine, Vol. 45, Issue 9 https://doi.org/10.1016/j.freeradbiomed.2008.08.007	journal	November 2008
Low levels of endogenous oxidative damage cluster levels in unirradiated viral and human DNAs Sutherland, Betsy M.; Bennett, Paula V.; Cintron, Nela S. Free Radical Biology and Medicine, Vol. 35, Issue 5 https://doi.org/10.1016/S0891-5849(03)00327-7	journal	September 2003
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes Hamanaka, Robert B.; Chandel, Navdeep S. Trends in Biochemical Sciences, Vol. 35, Issue 9 https://doi.org/10.1016/j.tibs.2010.04.002	journal	September 2010
Biological Consequences of Radiation-induced DNA Damage: Relevance to Radiotherapy Lomax, M. E.; Folkes, L. K.; O'Neill, P. Clinical Oncology, Vol. 25, Issue 10 https://doi.org/10.1016/j.clon.2013.06.007	journal	October 2013
Attempted base excision repair of ionizing radiation damage in human lymphoblastoid cells produces lethal and mutagenic double strand breaks Yang, Ning; Galick, Heather; Wallace, Susan S. DNA Repair, Vol. 3, Issue 10 https://doi.org/10.1016/j.dnarep.2004.04.014	journal	October 2004
Overexpression of enzymes that repair endogenous damage to DNA: Overexpression of DNA repair enzymes Frosina, Guido European Journal of Biochemistry, Vol. 267, Issue 8 https://doi.org/10.1046/j.1432-1327.2000.01266.x	journal	April 2000
Responses to ionizing radiation mediated by inflammatory mechanisms: Tissue responses in radiation pathology Mukherjee, Debayan; Coates, Philip J.; Lorimore, Sally A. The Journal of Pathology, Vol. 232, Issue 3 https://doi.org/10.1002/path.4299	journal	January 2014
Abasic sites preferentially form at regions undergoing DNA replication Ii, Paul D. Chastain; Nakamura, Jun; Rao, Shangbang The FASEB Journal, Vol. 24, Issue 10 https://doi.org/10.1096/fj.09-145276	journal	May 2010
Oxidatively induced DNA damage: Mechanisms, repair and disease Dizdaroglu, Miral Cancer Letters, Vol. 327, Issue 1-2 https://doi.org/10.1016/j.canlet.2012.01.016	journal	December 2012
Evaluation of Number Average Length Analysis in Quantifying Double Strand Breaks in Genomic DNAs ^† Sutherland, Betsy M.; Bennett, Paula V.; Georgakilas, Alexandros G. Biochemistry, Vol. 42, Issue 11 https://doi.org/10.1021/bi0205505	journal	March 2003
Dynamics and diversions in base excision DNA repair of oxidized abasic lesions Demple, Bruce; DeMott, Michael S. Oncogene, Vol. 21, Issue 58 https://doi.org/10.1038/sj.onc.1206178	journal	December 2002
Are endogenous clustered dna damages induced in human cells? Bennett, Paula V.; Cintron, Nela S.; Gros, Laurent Free Radical Biology and Medicine, Vol. 37, Issue 4 https://doi.org/10.1016/j.freeradbiomed.2004.05.004	journal	August 2004
Biomarkers of oxidative damage in cigarette smokers: Which biomarkers might reflect acute versus chronic oxidative stress? Seet, Raymond C. S.; Lee, Chung-Yung J.; Loke, Wai Mun Free Radical Biology and Medicine, Vol. 50, Issue 12 https://doi.org/10.1016/j.freeradbiomed.2011.03.019	journal	June 2011
Endogenous DNA damage clusters in human skin, 3-D model, and cultured skin cells Bennett, Paula V.; Cuomo, Noelle L.; Paul, Sunirmal Free Radical Biology and Medicine, Vol. 39, Issue 6 https://doi.org/10.1016/j.freeradbiomed.2005.05.008	journal	September 2005
Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer Vilenchik, M. M.; Knudson, A. G. Proceedings of the National Academy of Sciences, Vol. 100, Issue 22 https://doi.org/10.1073/pnas.2135498100	journal	October 2003
Base Excision Repair Processing of Radiation-induced Clustered DNA Lesions O. Blaisdell, J.; Harrison, L.; S. Wallace, S. Radiation Protection Dosimetry, Vol. 97, Issue 1 https://doi.org/10.1093/oxfordjournals.rpd.a006634	journal	September 2001
Tumors induce complex DNA damage in distant proliferative tissues in vivo Redon, C. E.; Dickey, J. S.; Nakamura, A. J. Proceedings of the National Academy of Sciences, Vol. 107, Issue 42 https://doi.org/10.1073/pnas.1008260107	journal	September 2010
Regulation of DNA repair throughout the cell cycle Branzei, Dana; Foiani, Marco Nature Reviews Molecular Cell Biology, Vol. 9, Issue 4 https://doi.org/10.1038/nrm2351	journal	February 2008
Mitochondria and cancer Wallace, Douglas C. Nature Reviews Cancer, Vol. 12, Issue 10 https://doi.org/10.1038/nrc3365	journal	September 2012
Accumulation of oxidatively induced clustered DNA lesions in human tumor tissues Nowsheen, Somaira; Wukovich, Rebecca L.; Aziz, Khaled Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 674, Issue 1-2 https://doi.org/10.1016/j.mrgentox.2008.09.010	journal	March 2009
Transfection of the Escherichia coli nth Gene into Radiosensitive Chinese Hamster Cells: Effects on Sensitivity to Radiation, Hydrogen Peroxide, and Bleomycin Sulfate Harrison, Lynn; Skorvaga, Milan; Cunningham, Richard P. Radiation Research, Vol. 132, Issue 1 https://doi.org/10.2307/3578330	journal	October 1992
Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review Lorimore, S. A.; Wright, E. G. International Journal of Radiation Biology, Vol. 79, Issue 1 https://doi.org/10.1080/0955300021000045664	journal	January 2003
Physiological Roles of Mitochondrial Reactive Oxygen Species Sena, Laura A.; Chandel, Navdeep S. Molecular Cell, Vol. 48, Issue 2 https://doi.org/10.1016/j.molcel.2012.09.025	journal	October 2012
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate Ward, Patrick S.; Thompson, Craig B. Cancer Cell, Vol. 21, Issue 3 https://doi.org/10.1016/j.ccr.2012.02.014	journal	March 2012
Instability and decay of the primary structure of DNA Lindahl, Tomas Nature, Vol. 362, Issue 6422 https://doi.org/10.1038/362709a0	journal	April 1993
Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells Dayal, Disha; Martin, Sean M.; Limoli, Charles L. Biochemical Journal, Vol. 413, Issue 1 https://doi.org/10.1042/BJ20071643	journal	June 2008
Quantitative proteomic analysis of mitochondrial proteins reveals prosurvival mechanisms in the perpetuation of radiation-induced genomic instability Thomas, Stefani N.; Waters, Katrina M.; Morgan, William F. Free Radical Biology and Medicine, Vol. 53, Issue 3 https://doi.org/10.1016/j.freeradbiomed.2012.03.025	journal	August 2012
Clustered DNA Damages Induced by X Rays in Human Cells Sutherland, Betsy M.; Bennett, Paula V.; Sutherland, John C. Radiation Research, Vol. 157, Issue 6 https://doi.org/10.1667/0033-7587(2002)157[0611:CDDIBX]2.0.CO;2	journal	June 2002

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59 BASIC BIOLOGICAL SCIENCES
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