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Research Article

On the Role of DNA Double-Strand Breaks in Toxicity and Carcinogenesis

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Pages 155-174 | Published online: 25 Sep 2008

References

  • Eastman A., Barry M. A. The origins of DNA breaks: a consequence of DNA damage, DNA repair, or apoptosis?. Cancer Invest 1992; 10: 229
  • Frankenberg-Schwager M., Frankenberg D., Blocher D., Harbich R., Adamczyk C. Irrepairable DNA double-strand breaks induced in eukaryotic cells by sparsely or densely ionizing radiation and their importance for cell killing. Mutat. Res. 1982; 96: 132
  • Borek C., Hall E. S. Induction and modulation of radiogenic transformation in mammalian cells. Radiation Carcinogenesis, Epidemiology and Biological Significance, J. D. Boice, J. F.J. Fraumeni. Raven Press, New York 1984; 292
  • Waldren C. A., Carrell L., Sognier M., Puck T. T. The measurement of X-ray mutagenesis in relation to human disease. Proc. Natl. Acad. Sci. U.S.A. 1986; 83: 4839
  • Bryant P. E., Riches A. C. Transformation of murine C3H 10T1/2 cells resulting from DNA double-strand breaks induced by a restriction endonuclease. Br. J. Cancer 1989; 60: 852
  • Elia M. C., DeLuca J. G., Bradley M. O. Significance and measurement of DNA double strand breaks in mammalian cells. Pharmacol. Then 1991; 51: 291
  • Bellamy C. O. C., Malcomson R. D. G., Harrison D. J., Wyllie A. H. Cell death in health and disease: the biology and regulation of apoptosis. Semin. Cancer Biol 1995; 6: 3
  • MacDonald R. R., Lees R. K. Programmed death of autoreactive thymocytes. Nature 1990; 343: 642
  • Barrett J. C., Preston G. Apoptosis and cellular senescence: forms of irreversible growth arrest. Apoptosis II: The Molecular Basis of Apoptosis in Disease, L. D. Tomei, F. O. Cope. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY 1994; 253
  • Zein N., Sinha A. M., McGahren W. J., Ellestad G. A. Calicheamicin γ1 an antitumor antibiotic that cleaves double-stranded DNA site specifically. Science 1988; 240: 1198
  • McAfee S. E., Ashley G. W. Modulation of neocarzinostatin-mediated DNA double strand damage by activating thiol: deuterium isotope effects. Nucleic Acids Res. 1992; 20: 805
  • Lutze L. H., Winegar R. A., Jostes R., Cross F. T., Cleaver J. E. Radon-induced deletions in human cells: role of nonhomologous strand rejoining. Cancer Res. 1992; 52: 5126
  • Absalon M. J., Kozarich J. W., Stubbe J. Sequence-specific double-strand cleavage of DNA by Fe bleomycin. I. The detection of sequence-specific double-strand breaks using hairpin oligonucleotides. Biochemistry 1995; 34: 2065
  • Absalon M. J., Wu W., Kozarich J. W., Stubbe J. Sequence-specific double-strand cleavage of DNA by Fe bleomycin. II. Mechanism and dynamics. Biochemistry 1995; 34: 2076
  • McKoy J. F., Pleninger P., Wall L., Pramanik A., Martinez M., Moore C. W. Genetic changes and bioassays in bleomycin- and phleomycin-treated cells, and their relationship to chromosomal breaks. Mutat. Res. 1995; 336: 19
  • Wassermann K. Intragenomic heterogeneity of DNA damage formation and repair: a review of cellular responses to covalent drug DNA interaction. Crit. Rev, Toxicol. 1994; 24: 281
  • Bradley M. O., Taylor V. I. DNA double strand breaks induced in normal human cells during the repair of ultraviolet light damage. Proc. Natl. Acad. Sci. U.S.A. 1981; 78: 3619
  • Darroudi F., Natarajan A. T. Cytogenetical characterization of Chinese hamster ovary X-ray-sensitive mutant cells xrs5 and xrs6. III. Induction of cell killing, chromosomal aberrations and sister-chroma-tid exchanges by bleomycin, mono- and bi-functional alkylating agents. Mutat. Res. 1989; 212: 123
  • Jeggo P. A. Studies on mammalian mutants defective in rejoining double-strand breaks in DNA. Mutat. Res. 1990; 239: 1
  • Siddiqui M. A., Bothe E. Single- and double-strand break formation in DNA irradiated in aqueous solution: dependence on dose and OH radical scavenger concentration. Racliat. Res. 1987; 112: 449
  • Ward J. F. The yield of DNA double-strand breaks produced intracellularly by ionizing radiation : a review. Int. J. Radiat. Biol 1990; 57: 1141
  • Toyokuni S., Sagripanti J. L. DNA single-and double-strand breaks produced by ferric nitrilotriacetate in relation to renal tubular carcinogenesis. Carcinogenesis 1993; 14: 223
  • Kappus H. Oxidative stress in chemical toxicity. Arch. Toxicol 1987; 60: 144
  • Marselos M., Vainio H. Carcinogenic properties of pharmaceutical agents evaluated in the IARC monographs programme. Carcinogenesis 1991; 12: 1751
  • Li Y., Trush M. A. DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation. Carcinogenesis 1993; 14: 1303
  • Bennett R. A., Swerdlow P. S., Povirk L. F. Spontaneous cleavage of bleomycin-induced abasic sites in chromatin and their mutagenicity in mammalian shuttle vectors. Biochemistry 1993; 32: 3188
  • Byrnes R. W., Petering D. H. Repair of bleomycin-induced DNA double-strand breakage in Ehrlich Ascites tumor cell. Radiat. Res. 1993; 134: 343
  • Byrnes R. W., Petering D. H. DNA strand breakage in isolated nuclei subjected to bleomycin or hydrogen peroxide. Biochem. Pharmacol 1994; 48: 575
  • Okada S., Midorikawa O. Induction of the rat renal adenocarcinoma by Fe-nitrilotriacetate. Jpn. Arch. Intern. Med. 1982; 36: 41
  • Li J. L., Okada S., Hamazaki S., Ebina Y., Midorikawa O. Subacute nephrotoxicity and induction of renal cell carcinoma in mice treated with ferric nitrilotriacetate. Cancer Res. 1987; 47: 1867
  • Inoue S., Kawanishi S. Hydroxyl radical production and human DNA damage induced by ferric nitrilotriacetate and hydrogen peroxide. Cancer Res. 1987; 47: 6522
  • Mahmood N., Khan S. G., Athar M., Rahman Q. Differential role of hydrogen peroxide and organic peroxides in augmenting asbestos-mediated DNA damage: implications for asbestos induced carcinogenesis. Biochem. Biophys. Res. Commun. 1994; 200: 687
  • Marczynski B., Czuppon A. B., Marek W., Reichel G., Baur X. Increased incidence of DNA double-strand breaks and anti-ds DNA antibodies in blood of workers occupationally exposed to asbestos. Hum. Exp. Toxicol 1994; 13: 3
  • Liu L. F. DNA topoisomerase poisons as antitumor drugs. Annu. Rev. Biochem. 1989; 58: 351
  • Anderson R. D., Berger N. A. Mutagenicity and carcinogenicity of topoisomerase-interactive agents. Mutat. Res. 1994; 309: 109
  • Sandoval C., Pui C. H., Bowman L. C., Heaton D., Hurwitz C. A., Raimondi S. C., Behm F. G., Head D. R. Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation. J. Clin. Oncol 1993; 11: 1039
  • Ryan J. J., Prochownik E., Gottlieb C. A., Apel I. J., Merino R., Nunez G., Clarke M. F. c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle. Proc. Natl. Acad. Sci. U.S.A. 1994; 91: 5878
  • Squires S., Ryan A. J., Strutt H. L., Johnson R. T. Hypersensitivity of Cockayne's syndrome cells to camptothecin is associated with the generation of abnormally high levels of double strand breaks in nascent DNA. Cancer Res. 1993; 53: 2012
  • Calabresi P., Chabner B. A. Chemotherapy of neoplastic diseases. Goodman and Gilman's the Pharmacological Basis of Therapeutics, A. G. Gilman, T. W. Rail, A. S. Nies, P. Taylor. Pergamon Press, New York 1991; 1202
  • Gillardeaux O., Perin-Rousel O., Perin F. Characterization by32P-postlabelling of 8-methoxy-psoralen adducts. IARC Scientific Publication: Postlabelling Methods for the Detection of DNA Damage, D. H. Phillips, M. Castegnaro, H. Bartsch. International Agency for Research on Cancer, Lyon 1993; 133
  • Payet D., Gaucheron F., Sip M., Leng M. Instability of the monofunctional adducts in cis-[Pt(NH3)2(N7-N-methyl-2-diazapyrenium)Cl2+-modi-fied DNA: rates of cross-linking reactions in cis-platinum-modified DNA. Nucleic Acids Res. 1993; 21: 5846
  • Dardalhon M., Averbeck D. Pulsed-field gel electrophoresis analysis of the repair of psoralen plus LfVA induced DNA photoadducts in Saccharomyces cerevisiae. Mutat. Res. 1995; 336: 49
  • Wang J. Y., Prorok G., Vaughan W. P. Cytotoxicity. DNA cross-linking, and DNA single-strand breaks induced by cyclophosphamide in a rat leukemia in vivo. Cancer Chemother. Pharmacol. 1993; 31: 381
  • Siegel D., Beall H., Senekowitsch C., Kasai M., Arai H., Gibson N. W., Ross D. Bioreductive activation of mitomycin C by DT-diaphorase. Biochemistry 1992; 31: 7879
  • Marczynski B., Czuppon A. B., Marek W., Baur X. Indication of DNA strand breaks in human white blood cells afterin vitro exposure to toluene diisocyanate (TDI). Toxicol. Inch Hlth 1992; 8: 157
  • Marczynski B., Czuppon A. B., Hoffarth H. P., Marek W., Baur X. DNA damage in human white blood cells after inhalative exposure to methylenediphenyl diisocyanate (MDI) – case report. Toxicol. Lett. 1992; 60: 131
  • Wang T. V., Smith K. C. Postreplication repair in ultraviolet-irradiated human fibroblasts: formation and repair of DNA double-strand breaks. Carcinogenesis 1986; 7: 389
  • Bradley M. O., Taylor V. I., Armstrong M. J., Galloway S. M. Relationships among cytotoxicity. lysosomal breakdown, chromosome aberrations. and DNA double-strand breaks. Mutat. Res. 1987; 189: 69
  • Nicotera P., Bellomo G., Orrenius S. The role of Ca:” in cell killing. Chem. Res. Toxicol. 1990; 3: 484
  • Nicotera P., Bellomo G., Orrenius S. Calcium-mediated mechanisms in chemically induced cell death. Anmt. Rev. Pharmacol. Toxicol. 1992; 32: 449
  • Orrenius S., McCabe M. J. J., Nicotera P. Ca:+-dependent mechanisms of cytotoxicity and programmed cell death. Toxicol. Lett. 1992; 64/65: 357
  • Zhivotovsky B., Wade D., Nicotera P., Orrenius S. Role of nucleases in apoptosis. Int. Arch. Allergy Immunol 1994; 105: 333
  • Zhivotovsky B., Wade D., Gahm A., Orrenius S., Nicotera P. Formation of 50 kbp chromatin fragments in isolated liver nuclei is mediated by protease and endonuclease activation. FEBS Lett. 1994; 351: 150
  • Stoler D. L., Anderson G. R., Russo C. A., Spina A. M., Beerman T. A. Anoxia-inducible endonuclease activity as a potential basis of the genomic instability of cancer cells. Cancer Res. 1992; 52: 4372
  • Anderson R. J., Sponsel H. T., Kroll D. J., Jackson S., Breckon R., Hoeffler J. P. Escape from the antiproliferative effect of transforming growth factor-fSl in LLC-PK1 renal epithelial cells. Kidney Int. 1994; 45: 642
  • Russo C. A., Weber T. K., Volpe C. M., Stoler D. L., Petrelli N. J., Rodriguezbigas M., Burhans W. C., Anderson G. R. An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer. Cancer Res. 1995; 55: 1122
  • Frankenberg-Schwager M., Frankenberg D., Harbich R., Adamczyk C. A comparative study of rejoining of DNA double-strand breaks in yeast irradiated with 3.5 MeV a-particles or with 30 MeV electrons. Int. J. Radiat. Biol 1990; 57: 1151
  • Anderson G. R., Stoler D. L., Scarcello L. A. Normal fibroblasts responding to anoxia exhibit features of the malignant phenotype. J. Biol. Chem. 1989; 264: 14885
  • Windle B., Draper B. W., Yin Y., O'Gorman S., Wahl G. M. A. A central role for chromosome breakage in gene amplification deletion formation. and amplicon integration. Genes Dew 1991; 5: 160
  • Windle B. E., Wahl G. M. Molecular dissection of mammalian gene amplification: new mechanistic insights revealed by analyses of very early events. Mutat. Res. 1992; 276: 199
  • Cheng K. C., Loeb L. A. Genomic instability and tumor progression: mechanistic considerations. Adv. Cancer Res. 1993; 60: 1211
  • Yin Y., Tainsky M. A., Bischoff F. Z., Strong L. C., Wahl G. M. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 1992; 70: 937
  • Muehlematter D., Larsson R., Cerutti P. Active oxygen induced DNA strand breakage and poly ADP-ribosylation in promotable and non-pro-motable JB6 mouse epidermal cells. Carcinogenesis 1988; 9: 239
  • Cerutti P., Larsson R., Krupitza G., Muehlematter D., Crawford D., Amstad P. Pathophysiological mechanisms of active oxygen. Mutat. Res. 1989; 214: 81
  • Corcoran G. B., Fix L., Jones D. P., Moslen M. T., Nicotera P., Oberhammer F. A., Buttyan R. Apoptosis: molecular control point in toxicity. Toxicol. Appl. Pharmacol 1994; 128: 169
  • Dypbukt J. M., Ankarcrona M., Burkitt M., Sjoholm A., Strom K., Orrenius S. Different prooxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F. The role of intracellular polyamines. J. Biol Chem. 1994; 269: 30553
  • Schulte-Hermann R., Graslkraupp B., Bursch W. Tumor development and apoptosis. Int. Arch. Allergy Immunol 1994; 105: 363
  • Barry M. A., Behnke C. A., Eastman A. Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem. Pharmacol 1990; 40: 2353
  • Stewart B. W. Mechanisms of apoptosis: integration of genetic, biochemical, and cellular indicators. J. Natl. Cancer Inst 1994; 86: 1286
  • McConkey D. J., Hartzell P., Nicotera P., Orrenius S. Calcium-activated DNA fragmentation kills immature thymocytes. FASEB J. 1989; 3: 1843
  • Lennon S. V., Cotter T. G. The regulatory role of zinc in apoptosis in human tumour cell lines. Biochem. Soc. Trans. 1992; 20: 78S
  • Lennon S. V., Kilfeather S. A., Cotter T. G. The role of calcium in the induction of apoptosis in human tumour cell lines. Biochem. Soc. Trans. 1992; 20: 77S
  • Ling Y. H., Priebe W., Perez-Soler R. Apoptosis induced by anthracycline antibiotics in P388 parent and multidrug-resistant cells. Cancer Res. 1993; 53: 1845
  • Davis M. A., Smith M. W., Chang S. H., Trump B. F. Characterization of a renal epithelial cell model of apoptosis using okadaic acid and the NRK-52E cell line. Toxicol. Pathol 1994; 22: 595
  • Bicknell G. R., Cohen G. M. Cleavage of DNA to large kilobase pair fragments occurs in some forms of necrosis as well as apoptosis. Biochem. Biophys. Res. Commun. 1995; 207: 40
  • Radford I. R. P53 status, DNA double-strand break repair proficiency, and radiation response of mouse lymphoid and myeloid cell lines. Int. J. Radial Biol. 1994; 66: 557
  • Bardeesy N., Beckwith J. B., Pelletier J. Clonal expansion and attenuated apoptosis in Wilms' tumors are associated with p53 gene mutations. Cancer Res. 1995; 55: 215
  • Xia F., Wang X., Wang Y. H., Tsang N. M., Yandell D. W., Kelsey K. T., Liber H. L. Altered p53 status correlates with differences in sensitivity to radiation-induced mutation and apoptosis in two closely related human lymphoblast lines. Cancer Res. 1995; 55: 12
  • Messmer U. K., Ankarcrona M., Nicotera P., Brune B. p53 expression in nitric oxide-induced apoptosis. FEBS Lett 1994; 355: 23
  • Schwartz J. L., Rotmensch J., Giovanazzi S., Cohen M. B., Weichselbaum R. R. Faster repair of DNA double-strand breaks in radioresistant human tumor cells. Int. J. Radiat. Oncol. Biol. Phys. 1988; 15: 907
  • Iliakis G., Metzger L., Muschel R. V., McKenna W. G. Induction and repair of DNA double strand breaks in radiation-resistant cells obtained by transformation of primary rat embryo cells with the oncogenes H-ras and v-myc. Cancer Res. 1990; 50: 6575
  • Ruiz de Almodovar J. M., Bush C., Peacock J. H., Steel G. G., Whitakker S. J., McMillan T. J. Dose-rate effect for DNA damage induced by ionizing radiation in human tumor cells. Radiat Res. 1994; 138: S93
  • Nunez M. I., Villalobos M., Olea N., Valenzuela M. T., Pedraza V., McMillan T. J., Dealmodovar J. M. R. Radiation-induced DNA double-strand break rejoining in human tumour cells. Br. J. Cancer 1995; 71: 311
  • Chen D. J., Marrone B. L., Nguyen T., Stackhouse M., Zhao Y., Siciliano M. J. Regional assignment of a human DNA repair gene (XRCC5) to 2q35 by X-ray hybrid mapping. Genomics 1994; 21: 423
  • Rathmell W. K., Chu G. Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks. Proc. Natl. Acad. Sci. U.S.A. 1994; 91: 7623
  • Muris D. F., Bezzubova O., Buerstedde J. M., Vreeken K., Balajee A. S., Osgood C. J., Troelstra C., Hoeijmakers J. H., Ostermann K., Schmidt H. Cloning of human and mouse genes homologous to RAD52, a yeast gene involved in DNA repair and recombination. Mutat. Res. 1994; 315: 295
  • Taccioli G. E., Gottlieb T. M., Blunt T., Priestly A., Demengeot J., Mizuta R., Lehmann A. R., Alt F., Jackson S. P., Jeggo P. A. Ku 80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 1994; 265: 1442
  • Troelstra C., Jaspers N. G. Recombination and repair. Ku starts at the end. Curr. Biol. 1994; 4: 1149
  • Bryant P. E. Rejoining and expression of radiation-induced DNA double-strand breaks in mammalian cells. Radiation Research 1895-1995. Congr. Proc. 10th Int. Congr. of Radiation Research in Wiirzburg, E. Hagen, H. Jung, C. Streffer. Universitatsdruckerei H. Stiirtz, Wiirzburg 1995; 48: S21/2
  • Ajmani A. K., Satoh M., Reap E., Cohen P. L., Reeves W. H. Absence of autoantigen Ku in mature human neutrophils and human promyelocytic leukemia line (HL-60) cells and lymphocytes undergoing apoptosis. J. Exp. Med. 1995; 181: 2049
  • Chen F. Q., Peterson S. R., Story M. D., Chen D. J. Disruption of DNA-PK in Ku80 mutant xrs-6 and the implications in DNA double-strand break repair. Mutat. Res. 1996; 362: 9
  • Kirchgessner C. U., Patil C. K., Evans J. W., Cuomo C. A., Fried L. M., Carter T., Oettinger M. A., Brown J. M. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 1995; 267: 1178
  • Li Z. Y., Otevrel T., Gao Y. J., Cheng H. L., Seed B., Stamato T. D., Taccioli G. E., Alt F. W. The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. Cell 1995; 83: 1079
  • Giaccia A. J., Denko N., MacLaren R., Mirman D., Waldren C., Hart I., Stamato T. D. Human chromosome 5 complements the DNA double-strand break-repair deficiency and gamma-ray sensitivity ot'theXR-1 hamster variant. Am. J. Hum. Genet 1990; 47: 459
  • Coquerelle T. M., Weibezahn K. F., Lucke-Huhlc C. Rejoining of double strand breaks in normal human and ataxia-teleangiectasia fibroblasts after exposure to 60Co gamma-rays, 241 Am alpha particles of bleomycin. Int. J. Radiat. Biol. 1987; 51: 209
  • Blöcher D., Sigut D., Hannan M. A. Fibroblasts from ataxia teleangiectasia (AT) and AT het-erozygotes show an enhanced level of residual DNA double-strand breaks after low dose-rate y-irradiation as assayed by pulse field gel electrophoresis. Int. J. Radiat. Biol. 1991; 60: 791
  • Swift M., Morrell D. D., Massey R. B., Chase C. L. incidence of cancer in 161 families affected by ataxia teleangiectasia, A'. Engl. J. Med. 1991; 325: 1831
  • Meyn M. S. Ataxia-telangiectasia and cellular responses to DNA damage. Cancer Res. 1995; 55: 5991
  • Strathern J. N., Shafer B. K., McGill C. B. DNA synthesis errors associated with double-strand-break repair. Genetics 1995; 140: 965
  • Löbrich M., Cooper P. K. An assay for determining double-strand break distribution and rejoining quality in specific genome locations. Radiation Research 1895–1995. Congr. Proc. 10th Int. Congr. of Radiation Research in Würzburg, E. Hagen, H. Jung, C. Streffer. Universitätsdruckerei H. Stürtz, Wüzburg 1995; 65, W01/1
  • Whitaker S. J., Lng Y. C., McMillan T. J. DNA double-strand break induction and rejoining as determinants of human tumour cell radiosensitivity. A pulsed-field gel electrophoresis study. Int. J. Radiat. Biol. 1995; 67: 7
  • Benjamin R., Gill D. M. Poly(ADP-ribose) synthesisin vitro programmed by damaged DNA. A comparison of DNA molecules containing different types of strand breaks. J. Biol. Chern. 1980; 255: 10502
  • Boulikas T. Poly(ADP-ribosyl)ation, DNA strand breaks, chromatin and cancer. Toxicol. Lett. 1993; 67: 129
  • Boulikas T. PoIy(ADP-ribose)synthesis in blocked and damaged cells and its relation to carcinogenesis. Anticancer Res. 1992; 12: 885
  • Sugimura T., Miwa M. Po Jy(ADP-ribose): historical perspective. Mol. Cell. Biochem. 1994; 138: 5
  • Vamvakas S., Bittner D., Dekant W., Anders M. W. Events that precede and that follow 5-(1.2-dichlorovinyl)-i.-cysteine-induced release of mitochondrial Ca2- and their association with cytotoxicity to renal cells. Biochem. Pharmacol. 1992; 44: 1131
  • Denda A., Ura H., Tsujiuchi T., Tsutsumi M., Eimoto H., Takashima Y., Kitazawa S., Kinugasa T., Konishi Y. Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis. Carcinogenesis 1989; 10: 1929
  • Singh N. A comparative study on the effect of tumor promoters on poly-ADP-ribosylation in A431 cells. Int. J. Cancer 1990; 46: 648
  • Singh N. Effect of tumour promoters on poly-ADP-ribosylation in human epidermoid carcinoma HeP2 cells. Int. J. Exp. Pathol 1990; 71: 809
  • Tsujiuchi T., Tsutsumi M., Denda A., Kondoh S., Nakae D., Maruyama H., Konishi Y. Possible involvement of poly ADP-ribosylation in phenobarbital promotion of rat hepatocarcinogenesis. Carcinogenesis 1990; II: 1783
  • Frankenberg-Schwager M. Induction, repair and biological relevance of radiation-induced lesions in eukaryotic cells. Radiat. Environ. Biophys. 1990; 29: 273
  • Phillips J. W., Morgan W. F. DNA-double strand breaks in mutagenesis. Environ. Mol. Mutagen. 1993; 22: 214
  • Borek C., Hall E. S., Rossi H. H. Malignant transformation in cultured hamster embryo cells produced by X-rays, 430keV monoenergetic neutrons. and heavy ions. Cancer Res. 1978; 38: 2997
  • Han A., Elkind M. M. Transformation of mouse C3H10T1/2 cells by singular and fractionated doses of X-rays and fission spectrum neutrons. Cancer Res. 1979; 39: 123
  • Robertson J. B., Koehler A., George J., Little J. B. Oncogenic transformation of mouse Bulb/3T3 cells by plutonium-238 alpha particles. Radiat. Res. 1983; 96: 261
  • Barendsen G. W., Gaiser J. F. Cell transformation in vitro by fast neutrons of different energies: implications for mechanism. Radiat. Protein Dosimetry 1985; 13: 145
  • Bertsche U., Iliakis G. Modifications in repair and expression of potentially lethal damage (oc-PLD) as measured by delayed plating or treatment with fi-araA in plateau-phase Ehrlich ascites tumor cells after exposure to charged particles of various specific energies. Radiat. Res. 1987; 111: 26
  • Hei T. K., Komatsu K., Hall E. J., Zaider M. Oncogenic transformation by charged particles of defined LET. Carcinogenesis 1988; 9: 747
  • Ostashevsky J. Y. Prediction of cell survival curves from DNA double-strand break repair data for low-and high-LET radiation. 1990; 523
  • Bauchinger M., Schmid E., Rimpl G., Kuhn H. Chromosome aberrations in human lymphocytes after irradiation with 15MeV neutrons in vitro. I. Dose response relation and RBE. Mutat. Res. 1975; 27: 103
  • Edwards A. A., Purrott R. J., Prosser J. S., Lloyd D. C. The induction of chromosome aberrations in human lymphocytes by alpha-radiation. Int. J. Radiat. Biol. 1980; 38: 83
  • Zoetelief J., Barendsen G. W. Dose-effect relationships for induction of cell inactivation and asymmetrical chromosome exchanges in three cell lines by photons and neutrons of different energy. Int. J. Radiat. Biol 1983; 43: 349
  • Thacker J., Wilkinson R. E., Goodhead D. T. The induction of chromosome exchange aberrations by carbon ultrasoft X-rays in V79 hamster cells. Int. J. Radiat. Biol 1986; 49: 645
  • Ottolenghi A., Merzagora M., Tallone L., Durante M., Paretzke H. G., Wilson W. E. The quality of DNA double-strand breaks: a Monte Carlo simulation of the end-structure of strand breaks produced by protons and alpha particles. Radiat. Environ. Biophys. 1995; 34: 239
  • Bryant P. E. Use of restriction endonucleases to study relationships between DNA double-strand breaks, chromosomal aberrations and other endpoints in mammalian cells. Int. J. Radiat. Biol 1988; 54: 869
  • Morgan W. F., Winegar R. A. The use of restriction endonucleases to study the mechanisms of chromosome damage. Chromosomal Aberrations: Basic and Applied Aspects, G. Obe, A. T. Natarajan. Springer-Verlag, Berlin 1989; 70
  • Bryant P. E., Birch D. A., Jeggo P. A. High chromosomal sensitivity of Chinese hamster xrs5 cells to restriction endonuclease induced DNA double-strand breaks. Int. J. Radiat. Biol 1987; 52: 537
  • Darroudi F., Natarajan A. T. Cytogenetical characterization of Chinese hamster ovary X-ray-sensitive mutant cells xrs5 and xrs6. IV. Study of chromosomal aberrations and sister-chromatid exchanges by restriction endonucleases and inhibitors of topoisomerase II. Mutat. Res. 1989; 212: 137
  • Jeggo R. A., Caldecott K., Pidsley S., Banks G. R. Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors. Cancer Res. 1989; 49: 7057
  • Evans H. H., Ricanati M., Horng M. F., Mencl J. Relationship between topoisomerase II and radiosensitivity in mouse L5178Y lymphoma strains. Mutat. Res. 1989; 217: 53
  • NAS/NRC, N. A. o. S. N. R. C. The effects on populations of exposure to low levels of ionizing radiation. Advisory Committee on the Biological Effects of Ionizing Radiation (BEIR). National Academy Press, Washington 1980
  • ICRP, I. C. o. R. P. Statement from the 1985 Paris Meeting of the International Commission on Radiological Protection. Health Phys. 1985, 48
  • NCRP, N. C. o. R. P. A. M. Recommendations on limits for exposure to ionizing radiation. National Council on Radiation Protection and Measurements, Bethesda, MD 1987, NCRP Report No. 91
  • NCRP, N. C. o. R. P. A. M. Relative biological efectiveness of radiations of different quality. National Council on Radiation Protection and Measurements, Bethesda, MD 1990, NCRP Report No. 104
  • Burkart W. Comparative toxicology: bases and limitations of comparing health effects from low level exposure to radiation and chemicals. Electricity and the Environment. IAEA International Atomic Energy Agency, Vienna 1991; 449
  • Bradley M. O., Kohn K. W. X-ray induced DNA double strand break production and repair in mammalian cells as measured by neutral filter elution. Nucleic Acids Res. 1979; 7: 793
  • McLaren J., Boulikas T., Vamvakas S. Induction of poly(ADP-ribosyl)ation in the kidney afterin vivo application of renal carcinogens. Toxicology 1994; 88: 101
  • Blocher D., Kunhi M. DNA double-strand break analysis by CHEF electrophoresis. Int. J. Radiat. Biol. 1990; 58: 23
  • Chu G. Pulsed field electrophoresis in contour-clamped homogeneous electric fields for the resolution of DNA by size or topology. Electrophoresis 1989; 10: 290
  • Blocher D., Einspenner M., Zajackowski J. CHEF electrophoresis, a sensitive technique for the determination of DNA double-strand breaks. Int. J. Radiat. Biol 1989; 56: 437
  • Erixon K., Cedervall B., Lewensohn R. Pulse-field gel electrophoresis for measuring radiation-induced DNA double-strand breaks. Comparison to the method of neutral filter elution. Ionizing Radiation Damage to DNA Molecular Aspects, S. S. Wallace, R. B. Painter. Wiley-Liss, New York 1990; 69
  • Ager D. D., Dewey W. C. Calibration of pulsed field gel electrophoresis for measurement of DNA double-strand breaks. Int. J. Radiat. Biol 1990; 58: 249
  • Iliakis G. E., Cicilioni O., Metzger L. Measurement of DNA double-strand breaks in CHO cells at various stages of the cell cycle using pulsed field gel electrophoresis: calibration by means of 1251 decay. Int. J. Radiat. Biol 1991; 59: 343
  • Cedervall B., Wong R., Albright N., Dynlacht J., Lambin P., Dewey W. C. Methods for the quantification of DNA double-strand breaks determined from the distribution of DNA fragment sizes measured by pulsed-field gel electrophoresis. Radiat. Res. 1995; 143: 8
  • Dhermain F., Dardalhon M., Queinnec E., Averbeck D. Induction of double-strand breaks in Chinese hamster ovary cells at two different dose rates of gamma-irradiation. Mutat. Res. 1995; 336: 161
  • Lauc G., Perovic S., Dapper J., Flögel M., Iskric S., Müller W. E. G. A non-radioactive, sensitive method for the detection of DNA fragmentation in apoptotic cells (rat pheochromocytoma PC 12 and rat cortical cells). Anal. Cell. Pathol 1994; 7: 107
  • Sestili P., Cattabeni F., Cantoni O. Simultaneous determination of DNA double strand breaks and DNA fragments size in cultured mammalian cells exposed to hydrogen peroxide/histidine or etoposide with CHEF electrophoresis. Carcinogenesis 1995; 16: 703
  • Olive P. L., Wlodek D., Banath J. P. DNA double-strand breaks measured in individual cells subjected to gel electrophoresis. Cancer Res. 1991; 51: 4671
  • McKelvey-Martin V. J., Green M. H. L., Schmezer P., Pool-Zobel B. L., De Méo M. P., Collins A. The single cell gel electrophoresis assay (comet assay): a European review. Mutat. Res. 1993; 288: 47
  • Olive P. L., Banath J. P. Radiation-induced DNA double-strand breaks produced in histone-de-pleted tumor cell nuclei measured using the neutral comet assay. Radial. Res. 1995; 142: 144
  • Ross G. M., McMillan T. J., Wilcox P., Collins A. R. The single cell microgel electrophoresis assay (comet assay): technical aspects and applications. Report on the 5th LH Gray Trust Workshop. Institute of Cancer Research. 1994. Mutat. Res. 1995; 337: 57
  • Tice R. R., Strauss G. H., Peters W. P. High-dose combination alkylating agents with autologous bone-marrow support in patients with breast cancer: preliminary assessment of DNA damage in individual peripheral blood lymphocytes using the single cell gel electrophoresis assay. Mutat. Res. 1992; 271: 101
  • Honchel R., Hailing K. C., Thibodeau S. N. Genomic instability in neoplasia. Semin. Cell Biol. 1995; 6: 45
  • Sorsa M., Wilbourn J., Vainio H. Human cytogenic damage as a predictor of cancer risk. Mechanisms of Carcinogenesis in Risk Identification – IARC Scientific Publications (WHO), H. Vainio, P. Magee, D. McGregor, A. J. McMichael. International Agency for Research on Cancer, Lyon 1992; Vol. 116: 543
  • Tobi S. E., Itzhaki R. F. DNA double-strand breaks measured by pulsed-field gel electrophoresis in irradiated lymphocytes from normal humans and those with Alzheimer's disease. Int. J. Radiat. Biol 1993; 63: 617
  • Okamoto A., Okabe M., Gomi K. Analysis of DNA fragmentation in human uterine cervix carcinoma HeLa S3 cells treated with duocarmycins or other antitumor agents by pulse field gel electrophoresis. Jpn. J. Cancer Res. 1994; 84: 93
  • Wang J., Delgado D. A., Deen D. F. Use of pulsed-field gel electrophoresis to investigate factors influencing the measurement of DNA double-strand breaks in human brain tumour specimens. Int. J. Radiat. Biol. 1995; 67: 153
  • Joos S., Fink T. M., Ratsch A., Lichter P. Mapping and chromosome analysis: the potential of fluorescence in situ hybridization. J. Biotechnol. 1994; 35: 135

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