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Hypoxia and Modulation of Cellular Radiation Response

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Molecular Determinants of Radiation Response

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Tumors possess many features that differentiate them from normal ­tissues which can potentially be targeted for therapy. One such difference is the presence of an inefficient vascular network, which is often unable to meet the tumor’s needs. The interaction of this faulty vascular system with the cells within the tumor leads to the development of a unique tumor microenvironment not found in normal tissues. This particular environment has a number of distinct features such as low oxygen concentrations, high interstitial fluid pressures and low pH. Previous studies have found that the presence of these microenvironmental conditions potentiates the development of certain adaptive responses by the tumor. These adaptive responses can have a number of adverse consequences, including increased resistance to chemo and radiotherapy. Nevertheless, since these microenvironmental characteristics are found in most solid tumor types, they have a profound effect on the tumor’s behavior and represent attractive therapeutic targets.

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References

  • Alarcon R, Koumenis C, Geyer RK et al (1999) Hypoxia induces p53 accumulation through MDM2 down-regulation and inhibition of E6-mediated degradation. Cancer Res 59:6046–6051

    PubMed  CAS  Google Scholar 

  • Alarcon RM, Denko NC, Giaccia AJ (2001) Genetic determinants that influence hypoxia-induced apoptosis. Novartis Found Symp 240:115–128

    PubMed  CAS  Google Scholar 

  • Bartek J, Lukas J (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3:421–429

    PubMed  CAS  Google Scholar 

  • Bencokova Z, Kaufmann MR, Pires IM et al (2009) ATM activation and signaling under hypoxic conditions. Mol Cell Biol 29:526–537

    PubMed  CAS  Google Scholar 

  • Bertrand P, Lambert S, Joubert C et al (2003) Overexpression of mammalian Rad51 does not stimulate tumorigenesis while a dominant-negative Rad51 affects centrosome fragmentation, ploidy and stimulates tumorigenesis, in p53-defective CHO cells. Oncogene 22:7587–7592

    PubMed  CAS  Google Scholar 

  • Bindra RS, Glazer PM (2007) Co-repression of mismatch repair gene expression by hypoxia in cancer cells: Role of the Myc/Max network. Cancer Lett 252:93–103

    PubMed  CAS  Google Scholar 

  • Bindra RS, Schaffer PJ, Meng A et al (2004) Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol 24:8504–8518

    PubMed  CAS  Google Scholar 

  • Bindra RS, Gibson SL, Meng A et al (2005) Hypoxia-induced down-regulation of BRCA1 expression by E2Fs. Cancer Res 65:11597–11604

    PubMed  CAS  Google Scholar 

  • Bindra RS, Crosby ME, Glazer PM (2007) Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev 26:249–260

    PubMed  CAS  Google Scholar 

  • Bristow RG, Hill RP (2008) Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8:180–192

    PubMed  CAS  Google Scholar 

  • Brizel DM, Scully SP, Harrelson JM et al (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943

    PubMed  CAS  Google Scholar 

  • Brown JM (1979) Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation. Br J Radiol 52:650–656

    PubMed  CAS  Google Scholar 

  • Brown JM (2002) Tumor microenvironment and the response to anticancer therapy. Cancer Biol Ther 1:453–458

    PubMed  Google Scholar 

  • Brown EJ, Baltimore D (2003) Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17:615–628

    PubMed  CAS  Google Scholar 

  • Brown JM, Giaccia AJ (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 58:1408–1416

    PubMed  CAS  Google Scholar 

  • Brown JM, Wilson WR (2004) Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4:437–447

    PubMed  CAS  Google Scholar 

  • Bryant HE, Schultz N, Thomas HD et al (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917

    PubMed  CAS  Google Scholar 

  • Cairns R, Papandreou I, Denko N (2006) Overcoming physiologic barriers to cancer treatment by molecularly targeting the tumor microenvironment. Mol Cancer Res 4:61–70

    PubMed  CAS  Google Scholar 

  • Cardenas-Navia LI, Mace D, Richardson RA et al (2008) The pervasive presence of fluctuating oxygenation in tumors. Cancer Res 68:5812–5819

    PubMed  CAS  Google Scholar 

  • Carney JP, Maser RS, Olivares H et al (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93:477–486

    PubMed  CAS  Google Scholar 

  • Chan N, Koritzinsky M, Zhao H et al (2008) Chronic hypoxia decreases synthesis of homologous recombination proteins to offset chemoresistance and radioresistance. Cancer Res 68:605–614

    PubMed  CAS  Google Scholar 

  • Choudhury A, Cuddihy A, Bristow RG (2006) Radiation and new molecular agents part I: targeting ATM-ATR checkpoints, DNA repair, and the proteasome. Semin Radiat Oncol 16:51–58

    PubMed  Google Scholar 

  • Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9:616–627

    PubMed  CAS  Google Scholar 

  • Coleman ML, Ratcliffe PJ (2009) Angiogenesis: escape from hypoxia. Nat Med 15:491–493

    PubMed  CAS  Google Scholar 

  • Collis SJ, DeWeese TL, Jeggo PA et al (2005) The life and death of DNA-PK. Oncogene 24:949–961

    PubMed  CAS  Google Scholar 

  • Costanzo V, Robertson K, Bibikova M et al (2001) Mre11 protein complex prevents double-strand break accumulation during chromosomal DNA replication. Mol Cell 8:137–147

    PubMed  CAS  Google Scholar 

  • Crosby ME, Devlin CM, Glazer PM et al (2009a) Emerging roles of microRNAs in the molecular responses to hypoxia. Curr Pharm Des 15:3861–3866

    PubMed  CAS  Google Scholar 

  • Crosby ME, Kulshreshtha R, Ivan M et al (2009b) MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res 69:1221–1229

    PubMed  CAS  Google Scholar 

  • D’Amours D, Jackson SP (2002) The Mre11 complex: at the crossroads of DNA repair and checkpoint signalling. Nat Rev Mol Cell Biol 3:317–327

    PubMed  Google Scholar 

  • Denko N, Wernke-Dollries K, Johnson AB et al (2003) Hypoxia actively represses transcription by inducing negative cofactor 2 (Dr1/DrAP1) and blocking preinitiation complex assembly. J Biol Chem 278:5744–5749

    PubMed  CAS  Google Scholar 

  • Economopoulou M, Langer HF, Celeste A et al (2009) Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med 15:553–558

    PubMed  CAS  Google Scholar 

  • Farmer H, McCabe N, Lord CJ et al (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921

    PubMed  CAS  Google Scholar 

  • Freiberg RA, Hammond EM, Dorie MJ et al (2006) DNA damage during reoxygenation elicits a Chk2-dependent checkpoint response. Mol Cell Biol 26:1598–1609

    PubMed  CAS  Google Scholar 

  • Gardner LB, Li F, Yang X et al (2003) Anoxic fibroblasts activate a replication checkpoint that is bypassed by E1a. Mol Cell Biol 23:9032–9045

    PubMed  CAS  Google Scholar 

  • Gibson SL, Bindra RS, Glazer PM (2005) Hypoxia-induced phosphorylation of Chk2 in an ataxia telangiectasia mutated-dependent manner. Cancer Res 65:10734–10741

    PubMed  CAS  Google Scholar 

  • Goodarzi AA, Jonnalagadda JC, Douglas P et al (2004) Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J 23:4451–4461

    PubMed  CAS  Google Scholar 

  • Graeber TG, Osmanian C, Jacks T et al (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379:88–91

    PubMed  CAS  Google Scholar 

  • Green SL, Freiberg RA, Giaccia AJ (2001) p21(Cip1) and p27(Kip1) regulate cell cycle reentry after hypoxic stress but are not necessary for hypoxia-induced arrest. Mol Cell Biol 21:1196–1206

    PubMed  CAS  Google Scholar 

  • Hammond EM, Denko NC, Dorie MJ et al (2002) Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 22:1834–1843

    PubMed  CAS  Google Scholar 

  • Hammond EM, Dorie MJ, Giaccia AJ (2003a) ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. J Biol Chem 278:12207–12213

    PubMed  CAS  Google Scholar 

  • Hammond EM, Green SL, Giaccia AJ (2003b) Comparison of hypoxia-induced replication arrest with hydroxyurea and aphidicolin-induced arrest. Mutat Res 532:205–213

    PubMed  CAS  Google Scholar 

  • Hammond EM, Dorie MJ, Giaccia AJ (2004) Inhibition of ATR leads to increased sensitivity to hypoxia/reoxygenation. Cancer Res 64:6556–6562

    PubMed  CAS  Google Scholar 

  • Heffernan TP, Simpson DA, Frank AR et al (2002) An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage. Mol Cell Biol 22:8552–8561

    PubMed  CAS  Google Scholar 

  • Helleday T, Lo J, van Gent DC et al (2007) DNA double-strand break repair: from mechanistic understanding to cancer treatment. DNA Repair (Amst) 6:923–935

    CAS  Google Scholar 

  • Hockel M, Schlenger K, Aral B et al (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515

    PubMed  CAS  Google Scholar 

  • Huang LE, Bindra RS, Glazer PM et al (2007) Hypoxia-induced genetic instability – a calculated mechanism underlying tumor progression. J Mol Med 85:139–148

    PubMed  CAS  Google Scholar 

  • Huen MS, Grant R, Manke I et al (2007) RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131:901–914

    PubMed  CAS  Google Scholar 

  • Hunt CR, Pandita RK, Laszlo A et al (2007) Hyperthermia activates a subset of ataxia-telangiectasia mutated effectors independent of DNA strand breaks and heat shock protein 70 status. Cancer Res 67:3010–3017

    PubMed  CAS  Google Scholar 

  • Jaakkola P, Mole DR, Tian YM et al (2001) Targeting of HIF-alpha to the von Hippel–Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468–472

    PubMed  CAS  Google Scholar 

  • Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461:1071–1078

    PubMed  CAS  Google Scholar 

  • Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    PubMed  CAS  Google Scholar 

  • Jeong I, Patel AY, Zhang Z et al (2010) Role of ataxia telangiectasia mutated in insulin signalling of muscle-derived cell lines and mouse soleus. Acta Physiol (Oxf) 98:465–475

    Google Scholar 

  • Kaelin WG, Jr. (2005) The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 5:689–698

    PubMed  CAS  Google Scholar 

  • Kaelin WG, Jr., Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30:393–402

    PubMed  CAS  Google Scholar 

  • Kim BM, Choi JY, Kim YJ et al (2007) Reoxygenation following hypoxia activates DNA-damage checkpoint signaling pathways that suppress cell-cycle progression in cultured human lymphocytes. FEBS Lett 581:3005–3012

    PubMed  CAS  Google Scholar 

  • Kolas NK, Chapman JR, Nakada S et al (2007) Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318:1637–1640

    PubMed  CAS  Google Scholar 

  • Koritzinsky M, Magagnin MG, van den Beucken T et al (2006) Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control. EMBO J 25:1114–1125

    PubMed  CAS  Google Scholar 

  • Koshiji M, To KK, Hammer S, Kumamoto K, Harris AL, Modrich P, Huang LE (2005) HIF-1alpha induces genetic instability by transcriptionally downregulating MutSalpha expression. Mol Cell 17:793–803

    PubMed  CAS  Google Scholar 

  • Koumenis C, Alarcon R, Hammond E et al (2001) Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol 21:1297–1310

    PubMed  CAS  Google Scholar 

  • Kovacs K, Toth A, Deres P et al (2004) Myocardial protection by selective poly(ADP-ribose) polymerase inhibitors. Exp Clin Cardiol 9:17–20

    PubMed  CAS  Google Scholar 

  • Lara PC, Lloret M, Clavo B et al (2008) Hypoxia downregulates Ku70/80 expression in cervical carcinoma tumors. Radiother Oncol 89:222–226

    PubMed  CAS  Google Scholar 

  • Lavin MF (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9:759–769

    PubMed  CAS  Google Scholar 

  • Lee JH, Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304:93–96

    PubMed  CAS  Google Scholar 

  • Li CY, Little JB, Hu K et al (2001) Persistent genetic instability in cancer cells induced by non-DNA-damaging stress exposures. Cancer Res 61:428–432

    PubMed  CAS  Google Scholar 

  • Liu SK, Coackley C, Krause M et al (2008) A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia. Radiother Oncol 88:258–268

    PubMed  CAS  Google Scholar 

  • Loeb LA (2001) A mutator phenotype in cancer. Cancer Res 61:3230–3239

    PubMed  CAS  Google Scholar 

  • Loehberg CR, Thompson T, Kastan MB et al (2007) Ataxia telangiectasia-mutated and p53 are potential mediators of chloroquine-induced resistance to mammary carcinogenesis. Cancer Res 67:12026–12033

    PubMed  CAS  Google Scholar 

  • Mailand N, Bekker-Jensen S, Faustrup H et al (2007) RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131:887–900

    PubMed  CAS  Google Scholar 

  • Martin SA, Lord CJ, Ashworth A (2008) DNA repair deficiency as a therapeutic target in cancer. Curr Opin Genet Dev 18:80–86

    PubMed  CAS  Google Scholar 

  • Martin-Oliva D, Aguilar-Quesada R, O’Valle F et al (2006) Inhibition of poly(ADP-ribose) polymerase modulates tumor-related gene expression, including hypoxia-inducible factor-1 activation, during skin carcinogenesis. Cancer Res 66:5744–5756

    PubMed  CAS  Google Scholar 

  • Maxwell PH, Wiesener MS, Chang GW et al (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275

    PubMed  CAS  Google Scholar 

  • Maya-Mendoza A, Petermann E, Gillespie DA et al (2007) Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J 26:2719–2731

    PubMed  CAS  Google Scholar 

  • McCabe N, Turner NC, Lord CJ et al (2006) Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res 66:8109–8115

    PubMed  CAS  Google Scholar 

  • Meng AX, Jalali F, Cuddihy A et al (2005) Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Radiother Oncol 76:168–176

    PubMed  CAS  Google Scholar 

  • Mihaylova VT, Bindra RS, Yuan J et al (2003) Decreased expression of the DNA mismatch repair gene Mlh1 under hypoxic stress in mammalian cells. Mol Cell Biol 23:3265–3273

    PubMed  CAS  Google Scholar 

  • Minchinton AI, Tannock IF (2006) Drug penetration in solid tumours. Nat Rev Cancer 6:583–592

    PubMed  CAS  Google Scholar 

  • Minter-Dykhouse K, Ward I, Huen MS et al (2008) Distinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis. J Cell Biol 181:727–735

    PubMed  CAS  Google Scholar 

  • Nordsmark M, Hoyer M, Keller J et al (1996a) The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas. Int J Radiat Oncol Biol Phys 35:701–708

    PubMed  CAS  Google Scholar 

  • Nordsmark M, Overgaard M, Overgaard J (1996b) Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 41:31–39

    PubMed  CAS  Google Scholar 

  • O’Neill P, Wardman P (2009) Radiation chemistry comes before radiation biology. Int J Radiat Biol 85:9–25

    PubMed  Google Scholar 

  • Pan Y, Oprysko PR, Asham AM et al (2004) p53 cannot be induced by hypoxia alone but responds to the hypoxic microenvironment. Oncogene 23:4975–4983

    PubMed  CAS  Google Scholar 

  • Pandita TK, Pandita S, Bhaumik SR (2009) Molecular parameters of hyperthermia for radiosensitization. Crit Rev Eukaryot Gene Expr 19:235–251

    PubMed  CAS  Google Scholar 

  • Pellegrini M, Celeste A, Difilippantonio S et al (2006) Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo. Nature 443:222–225

    PubMed  CAS  Google Scholar 

  • Petermann E, Maya-Mendoza A, Zachos G et al (2006) Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Mol Cell Biol 26:3319–3326

    PubMed  CAS  Google Scholar 

  • Pires IM, Bencokova Z, Milani M et al (2010) Effects of acute versus chronic hypoxia on dna damage responses and genomic instability. Cancer Res 70:925–935

    PubMed  CAS  Google Scholar 

  • Poon E, Harris AL, Ashcroft M (2009) Targeting the hypoxia-inducible factor (HIF) pathway in cancer. Expert Rev Mol Med 11:e26

    PubMed  Google Scholar 

  • Powell SN, Kachnic LA (2003) Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene 22:5784–5791

    PubMed  CAS  Google Scholar 

  • Quiles-Perez R, Munoz-Gamez JA, Ruiz-Extremera A et al (2010) Inhibition of poly adenosine diphosphate-ribose polymerase decreases hepatocellular carcinoma growth by modulation of tumor-related gene expression. Hepatology 51:255–266

    PubMed  CAS  Google Scholar 

  • Rankin EB, Giaccia AJ, Hammond EM (2009) Bringing H2AX into the angiogenesis family. Cancer Cell 15:459–461

    PubMed  CAS  Google Scholar 

  • Reichard P, Ehrenberg A (1983) Ribonucleotide reductase – a radical enzyme. Science 221:514–519

    PubMed  CAS  Google Scholar 

  • Reynolds TY, Rockwell S, Glazer PM (1996) Genetic instability induced by the tumor microenvironment. Cancer Res 56:5754–5757

    PubMed  CAS  Google Scholar 

  • Richard DJ, Bolderson E, Cubeddu L et al (2008) Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature 453:677–681

    PubMed  CAS  Google Scholar 

  • Sandhu JK, Haqqani AS, Birnboim HC (2000) Effect of dietary vitamin E on spontaneous or nitric oxide donor-induced mutations in a mouse tumor model. J Natl Cancer Inst 92:1429–1433

    PubMed  CAS  Google Scholar 

  • Shannon AM, Bouchier-Hayes DJ, Condron CM et al (2003) Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 29:297–307

    PubMed  CAS  Google Scholar 

  • Soengas MS, Alarcon RM, Yoshida H et al (1999) Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 284:156–159

    PubMed  CAS  Google Scholar 

  • Sprong D, Janssen HL, Vens C et al (2006) Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status. Int J Radiat Oncol Biol Phys 64:562–572

    PubMed  CAS  Google Scholar 

  • Stark JM, Pierce AJ, Oh J et al (2004) Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol Cell Biol 24:9305–9316

    PubMed  CAS  Google Scholar 

  • Stewart GS, Maser RS, Stankovic T et al (1999) The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99:577–587

    PubMed  CAS  Google Scholar 

  • Stiff T, Walker SA, Cerosaletti K et al (2006) ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J 25:5775–5782

    PubMed  CAS  Google Scholar 

  • Sugimura K, Takebayashi S, Taguchi H et al (2008) PARP-1 ensures regulation of replication fork progression by homologous recombination on damaged DNA. J Cell Biol 183:1203–1212

    PubMed  CAS  Google Scholar 

  • Syljuasen RG, Sorensen CS, Hansen LT et al (2005) Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol Cell Biol 25:3553–3562

    PubMed  CAS  Google Scholar 

  • To KK, Sedelnikova OA, Samons M et al (2006) The phosphorylation status of PAS-B distinguishes HIF-1alpha from HIF-2alpha in NBS1 repression. EMBO J 25:4784–4794

    PubMed  CAS  Google Scholar 

  • Um JH, Kang CD, Bae JH et al (2004) Association of DNA-dependent protein kinase with hypoxia inducible factor-1 and its implication in resistance to anticancer drugs in hypoxic tumor cells. Exp Mol Med 36:233–242

    PubMed  CAS  Google Scholar 

  • Uziel T, Lerenthal Y, Moyal L et al (2003) Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 22:5612–5621

    PubMed  CAS  Google Scholar 

  • Vaupel P, Harrison L (2004) Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist 9 Suppl 5:4–9

    PubMed  Google Scholar 

  • Wang B, Elledge SJ (2007) Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc Natl Acad Sci USA 104:20759–20763

    PubMed  CAS  Google Scholar 

  • Wardman P (2007) Chemical radiosensitizers for use in radiotherapy. Clin Oncol (R Coll Radiol) 19:397–417

    CAS  Google Scholar 

  • Wardman P (2009) The importance of radiation chemistry to radiation and free radical biology (The 2008 Silvanus Thompson Memorial Lecture). Br J Radiol 82:89–104

    PubMed  CAS  Google Scholar 

  • Yuan J, Narayanan L, Rockwell S et al (2000) Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to hypoxia and low pH. Cancer Res 60:4372–4376

    PubMed  CAS  Google Scholar 

  • Zou L, Elledge SJ (2003) Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300:1542–1548

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Center for Clinical Sciences Research, Stanford University, Stanford, CA, 94303-5152, USA

    Amato J. Giaccia

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  1. Ester M. Hammond
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  2. Monica Olcina
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  3. Amato J. Giaccia
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Correspondence to Amato J. Giaccia .

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  1. Dept. Radiation Oncology, Johns Hopkins University, N. Wolfe Street 600, Baltimore, 21287, Maryland, USA

    Theodore L. DeWeese

  2. Dept. Radiation Oncology, Johns Hopkins University, Orleans Street 1550, Baltimore, 21231, Maryland, USA

    Marikki Laiho

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Hammond, E.M., Olcina, M., Giaccia, A.J. (2011). Hypoxia and Modulation of Cellular Radiation Response. In: DeWeese, T., Laiho, M. (eds) Molecular Determinants of Radiation Response. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8044-1_6

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