Genetic and epigenetic features in radiation sensitivity. Part I: Cell signalling in radiation response

European Journal of Nuclear Medicine and Molecular Imaging

Volumn 32, Issue 2, 2005, Pages 229-246

  Bourguignon, Michel H ^a,b   Gisone, Pablo A ^c   Perez, Maria R ^c   Michelin, Severino ^c   Dubner, Diana ^c   Di Giorgio, Marina ^c   Carosella, Edgardo D ^b  

^a Dir Gen Surete Nucl R   (France)

^b SAINT LOUIS HOSPITAL   (France)

^c Autoridad Regulatoria Nuclear   (Argentina)

Author keywords

Cell signalling; DNA repair; Ionising radiation; Radiosensitivity

Indexed keywords

ATM PROTEIN; ATR PROTEIN; CERAMIDE; CYTOKINE; DNA; DNA DEPENDENT PROTEIN KINASE; GROWTH FACTOR; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROTEIN P53;

ACUTE GRANULOCYTIC LEUKEMIA; BIOSENSOR; BYSTANDER EFFECT; CANCER; CELL DEATH; CELL NUCLEUS; CHROMOSOMAL INSTABILITY; CYTOPLASM; DISEASE SEVERITY; DNA DAMAGE; DNA SEQUENCE; EPIGENETICS; EXCISION REPAIR; GENE AMPLIFICATION; GENE EXPRESSION; GENE IDENTIFICATION; GENE TARGETING; GENETIC SUSCEPTIBILITY; HOMOLOGOUS RECOMBINATION; HUMAN; HYPERSENSITIVITY; INFRARED RADIATION; IONIZING RADIATION; LEYDIG CELL; MISMATCH REPAIR; MOLECULAR MECHANICS; MYELODYSPLASTIC SYNDROME; NONHUMAN; OXIDATIVE STRESS; POINT MUTATION; PREDICTION; RADIOBIOLOGY; RADIOSENSITIVITY; REVIEW; SIGNAL TRANSDUCTION; STANDARD; TELOMERE;

ANIMALS; BYSTANDER EFFECT; CELL COMMUNICATION; DNA DAMAGE; DNA REPAIR; DOSE-RESPONSE RELATIONSHIP, RADIATION; EPIGENESIS, GENETIC; HUMANS; RADIATION DOSAGE; RADIATION TOLERANCE; RADIATION, IONIZING;

EID: 13844292453     PISSN: 16197070     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00259-004-1730-7     Document Type: Review

References (180)

1. Twardella D, Chang-Claude J. Studies on radiosensitivity from an epidemiological point of view - overview of methods and results. Radiother Oncol 2002;62:249-60.
2. Turreson I, Nyman J, Holmberg E, Odén A. Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys 1996;36:1065-75.
3. Marples B, Greco O, Joiner ML, Scott SD. Radiogenetic therapy: strategies to overcome tumor resistance. Curr Pharm Des 2003;9:2105-12.
4. Appleby JM, Barber JB, Levine E, Varley JM, Taylor AM, Stankovic T, et al. Absence of mutations in the ATM gene in breast cancer patients with severe response to radiotherapy. Br J Cancer 1997;76:1546-9.
5. Geara FB, Peters LJ, Ang KK, Garden AS, Tucker SL, Levy LB, et al. Comparison between normal tissue reactions and local tumor control in head and neck cancer patients treated by definitive radiotherapy. Int J Radiat Oncol Biol Phys 1996; 35:455-62.
6. Burnet NG, Nyman J, Turesson I, Wurm R, Yarnold JR, Peacock JH. The relationship between cellular radiation sensitivity and tissue response may provide the basis for individualising radiotherapy schedules. Radiother Oncol 1994;33:228-38.
7. Burnet NG, Nyman J, Turesson I, Wurm R, Yarnold JR, Peacock JH. Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular radiation sensitivity. Lancet 1992; 339:1570-1.
8. MacKay RI, Niemierko A, Goitein M., Hendry JH. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing. Radiother Oncol 1998;46:215-6.
9. Popanda O, Ebbeler R, Twardella D, Helmbold I, Gotzes F, Schmezer P, et al. Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy. Int J Radiat Oncol Biol Phys 2003;55:1216-25.
10. Alapetite C, Thirion P, de la Rochefordiere A, Cosset JM, Moustacchi E. Analysis by alkaline comet assay of cancer patients with severe reactions to radiotherapy: defective rejoining of radioinduced DNA strand breaks in lymphocytes of breast cancer patients. Int J Cancer 1999;83:83-90.
11. Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, et al. Localization of an-ataxia telangiectasia gene to chromosome 11q 22-23. Nature 1988;336:577-80.
12. Angele S, Romestaing P, Moullan N, Vuillaume M, Chapot B, Friesen M, et al. ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity. Cancer Res 2003;63:8717-25.
13. Sharp C, Cox R. Genetic susceptibility to radiation effects: possible implication for medical ionising radiation exposures. Eur J Nucl Med 1999;26:425-8.
14. Cosset JM, Moustacchi E. Tumor and individual radiosensitivity. An introduction. Cancer Radiother 1998;2:523-9.
15. Moustacchi E. DNA damage and repair: consequences on dose-responses. Mutat Res 2000;464:35-40.
16. Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature 2001;411:366-74.
17. Averbeck D. Mécanismes de réparation et mutagenèse radioinduite chez les eucaryotes supérieurs. Cancer Radiother 2000; 4:335-54.
18. Friedberg E. DNA damage and repair. Nature 2003; 421:436-40.
19. Christmann M, Tomicic M, Roos WP, Kaina B. Mechanisms of human DNA repair: an update. Toxicology 2003;193:3-34.
20. Hanawalt PC. Heterogeneity of DNA repair at the gene level. Mutat Res 1991;247:203-11.
21. Li GM, Modrich P. Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs. Proc Natl Acad Sci USA 1995; 92:1950-4.
22. Genschel J, Bazemore LR, Modrich P. Human exonuclease I is required for 5′ and 3′ mismatch repair. J Biol Chem 2002;277:13302-11.
23. Jiricny J, Nyström-Lahtti M. Mismatch repair defects in cancer. Curr Opin Genet Dev 2000;10:157-61.
24. Johnson RD, Jasin M. Double-strand-break-induced homologous recombination in mammalian cells. Biochem Soc Trans 2001;29:196-201.
25. Jackson S. Sensing and repairing DNA double-strand breaks. Carcinogenesis 2002;23:687-96.
26. Jeggo PA, Taccioli GE, Jackson SP. Ménage à trois: double strand break repair, V(D)J recombination and DNA-PK. Bioessays 1995;17:949-57.
27. Willers H, Dahm-Daphi J, Powell SN. Repair of radiation damage to DNA. Br J Cancer 2004;90:1297-301.
28. Ferguson DO, Alt FW. DNA double strand break repair and chromosomal translocation: lessons from animal models. Oncogene 2001;20:5572-9.
29. Blunt T, Finnie NJ, Taccioli GE, Smith GC, Demengeot J, Gotlieb TM, et al. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell 1995; 80:813-23.
30. UNSCEAR Report (2000) Sources and effects of ionising radiation, vol 2: effects. Annex F. Paragraph 34.
31. Wallace SS. Biological consequences of free radical-damaged DNA bases. Free Radic Biol Med 2002;33:1-14.
32. Davis TW, Wilson-Van Patten CR, Sharda N, Meyers M, Kinsella TJ, Boothman DA. DNA repair in higher eukaryotes. In: Nickoloff JA, Hoekstra M, editors. DNA damage and repair. Vol 2. Totowa: Human Press; 1998. p. 223-61.
33. Jackson SP. DNA-dependent protein kinase. Int J Biochem Cell Biol 1997;29:935-8.
34. Fei P, El-Deiry WS. P53 and radiation responses. Oncogene 2003;22:5774-83.
35. Shiloh Y. ATM and ATR: networking cellular responses to DNA damage. Curr Opin Genet Dev 2001;11:71-7.
36. Tibbetts RS, Brambaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY, et al. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev 1999; 13:152-7.
37. Carney JR Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR III, et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 1998; 93:477-86.
38. Michelson R, Weinert T. Sensor-less checkpoint activation? Nat Cell Biol 1999;1:E177-9.
39. Zou L, Cortez D, Elledge SJ. Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes Dev 2002;16:198-208.
40. Lucke-Huhle C. Alpha-irradiation-induced G2 delay: a period of cell recovery. Radiat Res 1982;89:298-308.
41. Anderson CW, Carter TH. The DNA-activated protein kinase-DNA-PK. Curr Top Microbiol Immunol 1996;217:91-111.
42. Jeggo PA. DNA-PK: at the cross-roads of biochemistry and genetics. Mutat Res 1997;384:1-14.
43. Ziegler M, Oei SL. A cellular survival switch:poly(ADP-ribosyl)ation stimulates DNA repair and silences transcription. Bioessays 2001;23:543-8.
44. Althaus FR, Kleczkowska HE, Malanga M, Muntener CR, Pleschke JM, Ebner M, et al. Poly ADP-ribosylation: a DNA break signal mechanism. Mol Cell Biochem 1999;193:5-11.
45. Satoh MS, Poirier GG, Lindahl T. Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage. Biochemistry 1994;33:7099-106.
46. Nyberg KA, Michelson RJ, Putnam CW, Weinert TA. Toward maintaining the genome: DNA damage and replication checkpoints. Annu Rev Genet 2002;36:617-56.
47. Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 2003;421:499-506.
48. Griffiths DJ, Barbet NC, McCready S, Lehmann AR, Carr AM. Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins. EMBO J 1995;14:5812-23.
49. Green CM, Erdjument-Bromage H, Tempst P, Lowndes NF. A novel Rad24 checkpoint protein complex closely related to replication factor C. Curr Biol 2000;10:39-42.
50. Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A. Purification and characterization of human DNA damage checkpoint Rad complexes. Proc Natl Acad Sci USA 2001; 98:11236-41.
51. Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, et al. Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Proc Natl Acad Sci U S A 2003;100:1633-8.
52. Petrini JH. The Mre11 complex and ATM: collaborating to navigate S phase. Curr Opin Cell Biol 2000;12:293-6.
53. Scully R, Livingston DM. In search of the tumour-suppressor functions of BRCA1 and BRCA2. Nature 2000;408:429-32.
54. Xu B, Kim St, Kastan MB. Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol 2001;21:3445-50.
55. Jongmans W, Vuillaume M, Chrzanowska K, Smeets D, Sperling K, Hall J. Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. Mol Cell Biol 1997; 17:5016-22.
56. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997;88:323-31.
57. Ko LJ, Prives C. p53: puzzle and paradigm. Genes Dev 1996;10:1054-72.
58. Sturzbecher HW, Donzelmann B, Henning W, Knippschild U, Buchhop S. p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction. EMBO J 1996;15:1992-2002.
59. Jongmans W, Vuillaume M, Kleijer WJ, Lakin ND, Hall J. The p53-mediated DNA damage response to ionizing radiation in fibroblasts from ataxia-without-telangiectasia patients. Int J Radiat Biol 1998 ;74:287-95.
60. Kachnic LA, Wu B, Wunsch H, Mekeel KL, DeFrank JS, Tang W, et al. The ability of p53 to activate downstream genes p21(WAF1/cip1) and MDM2, and cell cycle arrest following DNA damage is delayed and attenuated in scid cells deficient in the DNA-dependent protein kinase. J Biol Chem 1999; 274:13111-7.
61. Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 1999; 13:1501-12.
62. Dotto GP. p21(WAF1/Cip1): more than a break to the cell cycle? Biochim Biophys Acta 2000;1471:M43-56.
63. Zhou BB, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature 2000;408:433-9.
64. Lukas C, Bartkova J, Latella L, Falck J, Mailand N, Schroeder T, et al. DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology. Cancer Res 2001;61:4990-3.
65. Blattner C, Hay T, Meek DW, Lane DP. Hypophosphorylation of Mdm2 augments p53 stability. Mol Cell Biol 2002; 22:6170-82.
66. Caelles C, Helmberg A, Karin M. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature1994;370:220-3.
67. Wagner AJ, Kokontis JM, Hay N. Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1. Genes Dev 1994;8:2817-30.
68. Gao C, Tsuchida N. Activation of caspases in p53-induced transactivation-independent apoptosis. Jpn J Cancer Res 1999; 90:180-7.
69. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell 2003;11:577-90.
70. Benchimol S. p53-dependent pathways of apoptosis. Cell Death Differ 2001;8:1049-51.
71. Fei P, Bernhard EJ, El-Deiry WS. Tissue-specific induction of p53 targets in vivo. Cancer Res 2002;62:7316-27.
72. Neecke H, Lucchini G, Longhese MP. Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1- and Rad53-dependent checkpoint in budding yeast. EMBO J 1999;18:4485-97.
73. Vialard JE, Gilbert CS, Green CM, Lowndes NF. The budding yeast Rad9 checkpoint protein is subjected to Mec1/Tel1-dependent hyperphosphorylation and interacts with Rad53 after DNA damage. EMBO J 1998;17:5679-88.
74. Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ, et al. Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes Dev 2000;14:2989-3002.
75. Durocher D, Jackson SP. DNA-PK, ATM and ATR as sensors of DNA damage: variations on a theme? Curr Opin Cell Biol 2001;13:225-31.
76. Friedberg EC, Walker GC, Siede W. DNA Repair Mutagenesis. Washington: ASM; 1995.
77. Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, et al. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 1997;277:1497-501.
78. Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev 2000;14:1448-59.
79. Rhind N, Russell P. Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. J Cell Sci 2000;113:3889-96.
80. Gatei M, Scott SP, Filippovitch I, Soronika N, Lavin MF, Weber B, et al. Role for ATM in DNA damage-induced phosphorylation of BRCA1. Cancer Res 2000;60:3299-304.
81. Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, et al. Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 2000;406:210-5.
82. Wu X, Ranganathan V, Weisman DS, Heine WF, Ciccone DN, O'Neill TB, et al. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature 2000;405:477-82.
83. Iliakis G, Wang Y, Guan J, Wang H. DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogene 2003;22:5834-47.
84. Xu Y, Baltimore D. Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev 1996; 10:2401-10.
85. Furnari B, Rhind N, Russell P. Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. Science 1997; 277:1495-97.
86. Morgan SE, Lovly C, Pandita TK, Shiloh Y, Kastan MB. Fragments of ATM which have dominant-negative or complementing activity. Mol Cell Biol 1997;17:2020-9.
87. Liu ZG, Baskaran R, Lea-Chou ET, Wood LD, Chen Y, Karin M, et al. Three distinct signalling responses by murine fibroblasts to genotoxic stress. Nature 1996;384:273-6.
88. Chen YR, Wang X, Templeton D, Davis RJ, Tan TH. The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem 1996;271:31929-36.
89. Martinez JD, Pennington ME, Craven MT, Warters RL, Cress AE. Free radicals generated by ionizing radiation signal nuclear translocation of p53. Cell Growth Differ 1997;8:941-9.
90. Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993;75:241-51.
91. Kasid U, Suy S, Dent P, Ray S, Whiteside TL, Sturgill TW. Activation of Raf by ionizing radiation. Nature 1996;382: 813-6.
92. Sklar MD. The ras oncogenes increase the intrinsic resistance of NIH 3T3 cells to ionizing radiation. Science 1988;239: 645-7.
93. McKenna WG, Weiss MC, Endlich B, Ling CC, Bakanauskas VJ, Kelsten ML, et al. Synergistic effect of the v-myc oncogene with H-ras on radioresistance. Cancer Res 1990;50: 97-102.
94. Chiarugi V, Magnelli L, Cinelli M, Turchetti A, Ruggiero M. Dominant oncogenes, tumor suppressors, and radiosensitivity. Cell Mol Biol Res 1995;41:161-6.
95. Kolesnick R, Fuks Z. Radiation and ceramide-induced apoptosis. Oncogene 2003;22:5897-906.
96. Kulik G, Klippel A, Weber MJ. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol Cell Biol 1997;17(3):1595-606.
97. Friedlander RM, Gagliardini V, Rotello RJ, Yuan J. Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis. J Exp Med 1996;184:717-24.
98. Rodriguez C, Lacasse C, Hoang T. Interleukin-1 beta suppresses apoptosis in CD34 positive bone marrow cells through activation of the type I IL-1 receptor. J Cell Physiol 1996;166:387-96.
99. Braunschweiger PG, Basrur V, Santos O, Adessa A, Houdek P, Markoe AM. Radioresistance in murine solid tumors induced by interleukin-1. Radiat Res 1996;145:150-6.
100. Neta R, Oppenheim JJ, Wang JM, Snapper CM, Moorman MA, Dubois CM. Synergy of IL-1 and stem cell factor in radioprotection of mice is associated with IL-1 up-regulation of mRNA and protein expression for c-kit on bone marrow cells. J Immunol 1994;153:1536-43.
101. Neta R, Perlstein R, Vogel SN, Ledney GD, Abrams J. Role of interleukin 6 (IL-6) in protection from lethal irradiation and in endocrine responses to IL-1 and tumor necrosis factor. J Exp Med 1992;175:689-94.
102. Hallahan DE, Spriggs DR, Beckett MA, Kufe DW, Weichselbaum RR. Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation. Proc Natl Acad Sci U S A 1989;86:10104-7.
103. Hallahan DE, Beckett MA, Kufe D, Weichselbaum RR. The interaction between recombinant human tumor necrosis factor and radiation in 13 human tumor cell lines. Int J Radiat Oncol Biol Phys 1990;19:69-74.
104. Weichselbaum RR, Beckett MA, Vokes EE, Brachman DG, Haraf D, Hallahan D, et al. Cellular and molecular mechanisms of radioresistance. Cancer Treat Res 1995;74:131-40.
105. Nagata S. Apoptosis by death factor. Cell 1997;88:355-65.
106. Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 1996;274: 782-4.
107. Linard C, Marquette C, Mathieu J, Pennequin A, Clarencon D, Mathe D. Acute insuction of inflammatory cytokine expression after gamma irradiation in the rat:effect of an NF-κB inhibitor. Int J Radiat Biol Phys 2004;58:427-34.
108. Gorgojo L, Little JB. Expression of lethal mutations in the progeny of irradiated cells. Int J Radiat Biol 1989;55:619-30.
109. Seymour CB, Mothersill C, Alper T. High yields of lethal mutations in somatic mammalian cells that survive ionizing radiation. Int J Radiat Biol 1989;50:167-79.
110. Morgan W. Non-targeted and delayed effects of exposure to ionizing radiation: ionizing radiation induced genomic instability and bystander effects in vitro. Radiat Res 2003;159: 567-80.
111. Smith LE, Nagar S, King GJ, Morgan WF. Radiation-induced genomic instability: radiation quality and dose-response. Health Phys 2003;85:23-30.
112. Kaplan MI, Limoli CL, Morgan WF. Perpetuating radiation-induced chromosomal instability. Radiat Oncol Investig 1997;5:124-8.
113. Sinclair WK. X-ray induced heritable damage and small colony formation in cultured mammalian cells. Radiat Res 1964;21:584-611.
114. Chang WP, Little JB. Delayed reproductive death in X-irradiated Chinese hamster ovary cells. Int J Radiat Biol 1991;60: 483-96.
115. Manti L, Jamali M, Prise KM, Michael BD, Trott KR. Genomic instability in Chinese hamster cells after exposure to X-rays of alpha particles of different mean linear energy transfer. Radiat Res 1997;147:22-8.
116. Little JB, Nagasawa H, Pfenning T, Vetrous H. Radiation induced genomic instability:delayed mutagenic and cytogenetic effects of X-rays and alpha particles. Radiat Res 1997;148: 229-307.
117. Chang WP, Little JB. Delayed reproductive death as a dominant phenotype in cell clones surviving after X-irradiation. Carcinogenesis 1992;13:923-8.
118. Marder BA, Morgan WF. Delayed chromosomal instability induced by DNA damage. Mol Cell Biol 1993;13: 6667-77.
119. Rabbits TH. Chromosomal translocation in human cancer. Nature 1994;372:143-9.
120. Bedford JS, Mitchell JB, Griggs HG, Bender MA. Radiation induced cellular reproductive death and chromosome aberrations. Radiat Res 1978;76:573-86.
121. Sawant SG, Zheng W, Hopkins KM, Randers-Pehrson G, Lieberman HB, Hall EJ. The radiation-induced bystander effect for clonogenic survival. Radiat Res 2002;157:361-4.
122. Hahn P, Nevaldine B, Morgan WF. X-ray induction of methrotexate resistance due to dhfr gene amplification. Somat Cell Mol Genet 1990;16:413-23.
123. Sankaranarayanan K. Ionizing radiation and genetic risks. III. Nature of spontaneous and radiation-induced mutations in mammalian in vitro systems and mechanisms of induction of mutations by radiation. Mutat Res 1991;258:75-97.
124. Sankaranarayanan K. Ionizing radiation and genetic risks. II. Nature of spontaneous and radiation-induced mutations in mammalian in vitro systems and mechanisms of induction of mutations by radiation. Mutat Res 1991;258:51-73.
125. Nelson SL, Giver CR, Grosovsky AJ. Spectrum of X-ray-induced mutations in the HPRT gene. Carcinogenesis 1994;15: 495-502.
126. Little JB. Failla memorial lecture. Changing views of cellular radiosensitivity. Radiat Res 1994;140:299-311.
127. Limoli CL, Morgan WF. Genomic instability. Initiation and perpetuation. In: Hagen U, Harder D, Jung H, Streffer C, eds. Radiation research 1895-1995. Proceedings of the 10th International Congress of Radiation Research, vol 2. Würzburg, Germany, 1995.
128. Wojcik A, Bonk K, Muller WU, Streffer C. Do DNA double strand breaks induced by Alu I lead to development of novel aberrations in the second and third post-treatment mitosis? Radiat Res 1996;145:119-27.
129. Denko NC, Giaccia AJ, Stringer JR, Stambrook PG. The human Ha-ras oncogene induce genomic instability in murine fibroblasts within one cell cycle. Proc Natl Acad Sci U S A 1994;91:5124-8.
130. McKenna WG, Muschel RS, Gupta AK, Hahn SM, Bernhard EJ. The RAS signal transduction pathway and its role in radiation sensitivity. Oncogene 2003;22:5866-75.
131. Masson JY, Tarsouras MC, Stasiak AZ, Stasiak A, Shah R, Ilwraigth MC, et al. Identification and purification of two distinct complexes containing the five RAD51 paralogs. Gen Dev 2001;15:3296-307.
132. Tateishi S, Niwa H, Miyazaki JI, Fujimoto S, Inoue H, Yomaizumi M. Enhanced genomic instability and defective postreplication repair in RD 18 knockout mouse embryonic stem cells. Mol Cell Biol 2003;23:474-81.
133. 1 /S arrest following ionizing radiation. Mol Cell Biol 2002;22: 1819-33.
134. Morgan WF, Day JP, Kaplan MI, McGhee EM, Limoli CL. Genomic instability induced by ionizing radiation. Radiat Res 1996;146:247-58.
135. Bassing CH, Chua KF, Sekiguchi J, Suh H, Whitlow SR, Fleming JC, et al. Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX. Proc Natl Acad Sci U S A 2000;99:8173-8.
136. 136. Budworth H, Dianova II, Podust VN, Dianov GL. Repair of clustered DNA lesions. J Biol Chem 2002;277: 21300-5.
137. Day JP, Marder BA, Morgan WF. Telomeres and their possible role in chromosome stabilization. Environ Mol Mutagen 1993;22:245-9.
138. Obe G, Pfeiffer P, Savage JR, Johannes C, Goedecke W, Jeppesen P, et al. Chromosomal aberrations: formation, identification and distribution. Mutat Res 2002;504:17-36.
139. Bouffler SD, Blasco MA, Cox R, Smith PJ. Telomeric sequences, radiation sensitivity and genomic instability. Int J Radiat Biol 2001;77:995-1005.
140. Ducray C, Pommier JP, Martins L, Boussin F, Sabatier L. Telomere dynamics, end-to-end fusions and telomerase activation during the human fibroblast immortalization process. Oncogene 1999;18:4211-23.
141. Day JP, Limoli CL, Morgan WF. Recombination involving interstitial telomere repeat-like sequences promotes chromosomal instability in Chinese hamster cells. Carcinogenesis 1998;19:259-65.
142. Sabatier L, Lebeau J, Dutrillaux B. Chromosomal instability and alterations of telomeric repeats in irradiated human fibroblasts. Int J Radiat Biol 1994;66:611-3.
143. Limoli CL, Corcoran JJ, Milligan JR, Ward JF, Morgan WF, Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation. Radiat Res 1999;151:677-85.
144. Limoli CL, Pomai B, Corcoran JJ, Giedzinsk E, Kaplan MI, Hartmann A, et al. Genomic instability induced by high and low LET ionizing radiation. Adv Space Res 2000;25: 2107-17.
145. Grosovsky A, Bethel H, Pars K, Ritter L, Giver C, Gamy S, et al. Genomic instability in human lymphoid cells exposed to 1 Gev/amu Fe ions. Phys Med 2001;17:238-40.
146. Sawant SG, Randers-Pehrson G, Geard CR, Brenner DJ, Hall EJ. The bystander effect in radiation oncogenesis: I. Transformation in C3H10T1/2 cells in vitro can be initiated in the unirradiated neighbors of irradiated cells. Radiat Res 2001; 155:397-401.
147. Morgan WF. Non-targeted and delayed effects of exposure to ionizing radiaton: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects. Radiat Res 2003;159:581-96.
148. Tawn EJ, Whitehouse CA, Martin FA. Sequential chromosome aberration analysis following radiotherapy. No evidence for enhanced genomic instability. Mutat Res 2000;465:45-51.
149. Whitehouse CA, Tawn EJ, Martin FA, Riddel AE. Chromosome aberrations in radiation workers with internal deposits of plutonium. Radiat Res 1998;150:459-68.
150. Nakanishi M, Tanaka K, Shintani T, Takahashi T, Kamada N. Chromosomal instability in acute myelocytic leukemia and myelodysplastic syndrome patients among atomic bomb survivors. J Radiat Res (Tokyo) 1999;40:159-67.
151. Djordjevic B. Bystander effects: a concept in need of clarification . Bioessays 2000;22:286-90.
152. Belyakov OV, Malcolmson AM, Folkard M, Prise KM, Michael BD. Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts. Br J Cancer 2001;84:674-9.
153. Folakard M, Vojnovic B, Prise KM, Bowey AG, Locke RJ, Schettino G, Michael B. A charged-particle microbeam: I. Development of an experimental system for targeting cells individually with counted particles. Int J Radiat Biol 1997; 72:375-85.
154. Zhou H, Randers-PehrsonG, Waldren CA, Vannais D, Hall EJ, Hei TK. Induction of bystander mutagenic effect of alpha particles in mammalian cells. Proc Natl Acad Sci USA 2000;97:2099-114.
155. Belyakov OV, Folkard M, Mothersill C. A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation. Br J Cancer 2003;84:767-74.
156. Mothersill C, Seymour CB. Bystander and delayed effects after fractionated radiation exposure. Radiat Res 2002;158:626-33.
157. Lyng FM, Seymour CB, Mothersill C. Production of a signal by irradiated cells which lead to a response in unirradiated cells characteristic of initiation of apoptosis. Br J Cancer 2000;83:1223-30.
158. Lewis DA, Mayhugh BM, Qin Y, Trott K, Mendonca MS. Production of delayed death and neoplastic transformation of CGL1 cells by radiation-induced bystander effects. Radiat Res 2001;156:251-8.
159. Seymour CB, Mothersill C. Delayed expression of lethal mutations and genomic instability in the progeny of human epithelial cells that survived in a bystander-killing environment. Radiat Oncol Invest 1997;5:106-10.
160. 2 particles in the Chinese hamster. Radiat Res 1983;96:135-51.
161. Barcellos-Hoff MH, Brooks AL. Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects and genomic instability. Radiat Res 2001;156:618-27.
162. Rugo RE, Secretan MB, Schiestl RH. X-radiation causes a persistent induction of reactive oxygen species and a delayed reinduction of TP53 in normal human diploid fibroblasts. Radiat Res 158:210-9.
163. Clutton SM, Townsend KM, Walker C, Ansell JD, Wright EG. Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures. Carcinogenesis 1996;17:1633-9.
164. Tulard A, Hoffschir F, Hillariet de Boisferon F, Luccioni C, Bravard A. Persistent oxidative stress after ionizing radiation is involved in inherited radiosensitivity. Free Rad Biology Med 2003;35:68-77.
165. Tharmickal BL, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol 2000;279:1005-28.
166. Kamata H, Hirata H. Redox regulation of cellular signalling. Cell Signal 1999;11:1-14.
167. Heinloth AN, Shackelford RE, Innes CL, Bennet L, Li L, Amin RP, et al. ATM-dependent and independent gene expression changes in response to oxidative stress, gamma radiation and UV radiation. Radiat Res 2003;160:273-90.
168. Lorimore SA, Wright EG. Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? Int J Radiat Biol 2003;79:15-25.
169. Wink DA, Hanbauer I, Grisham MB, Laval F, Nims RW, Laval J, et al. Chemical biology of nitric oxide. Regulation and protective and toxic mechanisms. Curr Top Cell Regul 1996;34:159-87.
170. Matsumoto H, Hayashi S, Hatashita M, Ohnishi K, Shioura H, Ohtsubo T, et al. Induction of radioresistance by nitric oxide mediated bystander effect. Radiat Res 2001;155: 387-96.
171. Shao C, Stewart V, Folkard M, Michael BD, Prise KM. Nitric oxide mediated signaling in the bystander response of individually targeted glioma cells. Cancer Res 2003;63:8437-42.
172. Randers-Pehrson G, Geard CR, Johnson G, Elliston CD, Brener DJ. The Columbia University single-ion microbeam. Radiat Res 2001;156:210-4.
173. Morgan WF. Is there a common mechanism underlying genomic instability, bystander effects and other non targeted effects of exposure to ionizing radiation? Oncogene 2003;22:7094-9.
174. Olive PL, Banath JP. Phosphorylation of histone H2AX as a measure of radiosensitivity. Int J Radiat Oncol Biol Phys 2004;58:331-5.
175. Branner TB, Gupta AK, Shi Y, Hahn SM, Muschel RJ, McKenna WG, et al. Farnesyltransferase inhibition as radiation sensitizers. Int J Radiat Biol 2003;79:569-76.
176. Tutt A, Connor F, Bertwhistle D, Kerr P, Peacock J, Ross G, et al. Cell cycle genetic background dependence of the effect of loss of BRCA2 on ionizing radiation sensitivity. Oncogene 2003;22:2926-31.
177. Milas L, Mason KA, Ang KK. Epidermal growth factor receptor and its inhibition in radiotherapy: in vivo findings. Int J Radiat Biol 2003;79:539-45.
178. Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Saito S, et al. Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku 70 expression. J Exp Cancer Res 2003;22:223-8.
179. Harima Y, Sawada S, Miyazaki Y, Kin K, Ishihara H, Inamura M, et al. Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival. Am J Clin Oncol 2003;26:80-5.
180. Khodarev NN, Beckett M, Labay E, Darga T, Roizman B, Weichselbaum RR. STAT-1 is overexpressed in tumors selected for radio resistance and confer protection from radiation in transduced sensitive cells. PNAS 2004;101:1714-9.