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Hyperthermic Oncology from Bench to Bedside pp 19–32Cite as

Molecular Damage: Hyperthermia Alone

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Abstract

The goal of cancer therapy using hyperthermia is to kill cancer cells and shrink tumors directly. Understanding the molecular targets for heat-induced cell killing, and how such targets are protected or repaired in heat-resistant cells, might provide clues to improve cancer therapy with hyperthermia. However, the molecular mechanisms involved in heat-induced cell killing are not yet fully understood. This chapter is intended to provide an overview of hyperthermia-induced molecular damage to important cellular components such as proteins, lipids, and DNA. We will focus on heat-induced DNA damage, review recent literature, and discuss the potential issues and problems that remain to be solved to understand this process fully.

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References

  1. Roti Roti JL. Cellular responses to hyperthermia (40–46 degrees C): cell killing and molecular events. Int J Hyperthermia. 2008;24:3–15.

    Article  PubMed  Google Scholar 

  2. Falk MH, Issels RD. Hyperthermia in oncology. Int J Hyperthermia. 2001;17:1–18.

    Article  CAS  PubMed  Google Scholar 

  3. Takahashi A, Mori E, Ohnishi T. Heat-induced DNA damage. In: Shimizu T, Kondo T, editors. Cellular response to physical stress and therapeutic application. New York: Nova Science Publishers Inc.; 2013. p. 135–47.

    Google Scholar 

  4. Richter K, Haslbeck M, Buchner J. The heat shock response: life on the verge of death. Mol Cell. 2010;40:253–66.

    Article  CAS  PubMed  Google Scholar 

  5. Nakahata K, Miyakoda M, Suzuki K, Kodama S, Watanabe M. Heat shock induces centrosomal dysfunction, and causes non-apoptotic mitotic catastrophe in human tumour cells. Int J Hyperthermia. 2002;18:332–43.

    Article  CAS  PubMed  Google Scholar 

  6. Roti Roti JL, Kampinga HH, Malyapa RS, Wright WD, van der Waal RP, Xu M. Nuclear matrix as a target for hyperthermic killing of cancer cells. Cell Stress Chaperones. 1998;3:245–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sonna LA, Fujita J, Gaffin SL, Lilly CM. Invited review: effects of heat and cold stress on mammalian gene expression. J Appl Physiol. 2002;92:1725–42.

    Article  CAS  PubMed  Google Scholar 

  8. Henle KJ, Warters RL. Heat protection by glycerol in vitro. Cancer Res. 1982;42:2171–6.

    CAS  PubMed  Google Scholar 

  9. Morimoto RI, Kline MP, Bimston DN, Cotto JJ. The heat-shock response: regulation and function of heat-shock proteins and molecular chaperones. Essays Biochem. 1997;32:17–29.

    CAS  PubMed  Google Scholar 

  10. Rossi A, Ciafre S, Balsamo M, Pierimarchi P, Santoro MG. Targeting the heat shock factor 1 by RNA interference: a potent tool to enhance hyperthermochemotherapy efficacy in cervical cancer. Cancer Res. 2006;66:7678–85.

    Article  CAS  PubMed  Google Scholar 

  11. Burdon RH. Thermotolerance and the heat shock proteins. Symp Soc Exp Biol. 1987;41:269–83.

    CAS  PubMed  Google Scholar 

  12. Takahashi A, Yamakawa N, Mori E, Ohnishi K, Yokota S, Sugo N, et al. Development of thermotolerance requires interaction between polymerase-beta and heat shock proteins. Cancer Sci. 2008;99:973–8.

    Article  CAS  PubMed  Google Scholar 

  13. Anckar J, Sistonen L. Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem. 2011;80:1089–115.

    Article  CAS  PubMed  Google Scholar 

  14. Fahy E, Subramaniam S, Murphy RC, Nishijima M, Raetz CR, Shimizu T, et al. Update of the LIPID MAPS comprehensive classification system for lipids. J Lipid Res. 2009;50:S9–14.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bruskov VI, Malakhova LV, Masalimov ZK, Chernikov AV. Heat-induced formation of reactive oxygen species and 8-oxoguanine, a biomarker of damage to DNA. Nucleic Acids Res. 2002;30:1354–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hall DM, Buettner GR, Matthes RD, Gisolfi CV. Hyperthermia stimulates nitric oxide formation: electron paramagnetic resonance detection of.NO-heme in blood. J Appl Physiol. 1994;77:548–53.

    CAS  PubMed  Google Scholar 

  17. Yoshikawa T, Kokura S, Tainaka K, Itani K, Oyamada H, Kaneko T, et al. The role of active oxygen species and lipid peroxidation in the antitumor effect of hyperthermia. Cancer Res. 1993;53:S2326–9.

    Google Scholar 

  18. Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr. 1993;57:S715–24.

    Google Scholar 

  19. Chen JJ, Yu BP. Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radic Biol Med. 1994;117:411–18.

    Article  Google Scholar 

  20. Spickett CM, Reglinski J, Smith WE, Wilson R, Walker JJ, McKillop J. Erythrocyte glutathione balance and membrane stability during preeclampsia. Free Radic Biol Med. 1998;24:1049–55.

    Article  CAS  PubMed  Google Scholar 

  21. Bates DA, Le Grimellec C, Bates JH, Loutfi A, Mackillop WJ. Effects of thermal adaptation at 40 degrees C on membrane viscosity and the sodium-potassium pump in Chinese hamster ovary cells. Cancer Res. 1985;45:4895–9.

    CAS  PubMed  Google Scholar 

  22. Gerner EW, Cress AE, Stickney DG, Holmes DK, Culver PS. Factors regulating membrane permeability alter thermal resistance. Ann N Y Acad Sci. 1980;335:215–33.

    Article  CAS  PubMed  Google Scholar 

  23. Lecavalier D, Mackillop WJ. The effect of hyperthermia on glucose transport in normal and thermal-tolerant Chinese hamster ovary cells. Cancer Lett. 1985;29:223–31.

    Article  CAS  PubMed  Google Scholar 

  24. Bates DA, Mackillop WJ. Hyperthermia, adriamycin transport, and cytotoxicity in drug-sensitive and -resistant Chinese hamster ovary cells. Cancer Res. 1986;46:5477–81.

    CAS  PubMed  Google Scholar 

  25. Oei AL, Vriend LE, Crezee J, Franken NA, Krawczyk PM. Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all. Radiat Oncol. 2015;10:165. doi:10.1186/s13014-015-0462-0.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Corry PM, Robinson S, Getz S. Hyperthermic effects on DNA repair mechanisms. Radiology. 1977;123:475–82.

    Article  CAS  PubMed  Google Scholar 

  27. Warters RL, Brizgys LM. Apurinic site induction in the DNA of cells heated at hyperthermic temperatures. J Cell Physiol. 1987;133:144–50.

    Article  CAS  PubMed  Google Scholar 

  28. Lindahl T, Nyberg B. Heat-induced deamination of cytosine residues in deoxyribonucleic acid. Biochemistory. 1974;13:3405–10.

    Article  CAS  Google Scholar 

  29. Wong RS, Kapp LN, Krishnaswamy G, Dewey WC. Critical steps for induction of chromosomal aberrations in CHO cells heated in S phase. Radiat Res. 1993;133:52–9.

    Article  CAS  PubMed  Google Scholar 

  30. Warters RL, Henle KJ. DNA degradation in Chinese hamster ovary cells after exposure to hyperthermia. Cancer Res. 1982;42:4427–32.

    CAS  PubMed  Google Scholar 

  31. Dikomey E. Effect of hyperthermia at 42 and 45 degrees C on repair of radiation-induced DNA strand breaks in CHO cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1982;41:603–14.

    Article  CAS  PubMed  Google Scholar 

  32. Jorritsma JB, Konings AW. The occurrence of DNA strand breaks after hyperthermic treatments of mammalian cells with and without radiation. Radiat Res. 1984;98:198–208.

    Article  CAS  PubMed  Google Scholar 

  33. Mitchel RE, Birnboim HC. Triggering of DNA strand breaks by 45 degrees C hyperthermia and its influence on the repair of gamma-radiation damage in human white blood cells. Cancer Res. 1985;45:2940–5.

    Google Scholar 

  34. Anai H, Maehara Y, Sugimachi K. In situ nick translation method reveals DNA strand scission in HeLa cells following heat treatment. Cancer Lett. 1988;40:33–8.

    Article  CAS  PubMed  Google Scholar 

  35. Wong RS, Dynlacht JR, Cedervall B, Dewey WC. Analysis by pulsed-field gel electrophoresis of DNA double-strand breaks induced by heat and/or X-irradiation in bulk and replicating DNA of CHO cells. Int J Radiat Biol. 1995;68:141–52.

    Article  CAS  PubMed  Google Scholar 

  36. Takahashi A, Matsumoto H, Nagayama K, Kitano M, Hirose S, Tanaka H, et al. Evidence for the involvement of double-strand breaks in heat-induced cell killing. Cancer Res. 2004;64:8839–45.

    Article  CAS  PubMed  Google Scholar 

  37. Velichko AK, Petrova NV, Kantidze OL, Razin SV. Dual effect of heat shock on DNA replication and genome integrity. Mol Biol Cell. 2012;23:3450–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273:5858–68.

    Article  CAS  PubMed  Google Scholar 

  39. Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol. 2000;10:886–95.

    Article  CAS  PubMed  Google Scholar 

  40. Sedelnikova OA, Rogakou EP, Panyutin IG, Bonner WM. Quantitative detection of 125IdU-induced DNA double-strand breaks with gamma-H2AX antibody. Radiat Res. 2002;158:486–92.

    Article  CAS  PubMed  Google Scholar 

  41. Rothkamm K, Lobrich M. Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci U S A. 2003;100:5057–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Takahashi A, Ohnishi T. Does γH2AX foci formation depend on the presence of DNA double strand breaks? Cancer Lett. 2005;229:171–9.

    Article  CAS  PubMed  Google Scholar 

  43. Zhou C, Li Z, Diao H, Yu Y, Zhu W, Dai Y, et al. DNA damage evaluated by γH2AX foci formation by a selective group of chemical/physical stressors. Mutat Res. 2006;604:8–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dong Z, Hu H, Chen W, Li Z, Liu G, Yang J. Heat shock does not induce γH2AX foci formation but protects cells from N-methyl-N’-nitro-N-nitrosoguanidine-induced genotoxicity. Mutat Res. 2007;629:40–8.

    Article  CAS  PubMed  Google Scholar 

  45. Takahashi A, Mori E, Somakos GI, Ohnishi K, Ohnishi T. Heat induces γH2AX foci formation in mammalian cells. Mutat Res. 2008;656:88–92.

    Article  CAS  PubMed  Google Scholar 

  46. Kaneko H, Igarashi K, Kataoka K, Miura M. Heat shock induces phosphorylation of histone H2AX in mammalian cells. Biochem Biophys Res Commun. 2005;328:1101–6.

    Article  CAS  PubMed  Google Scholar 

  47. Paul C, Murray AA, Spears N, Saunders PT. A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction. 2008;136:73–84.

    Article  CAS  PubMed  Google Scholar 

  48. Takahashi A, Mori E, Su X, Nakagawa Y, Okamoto N, Uemura H, et al. ATM is the predominant kinase involved in the phosphorylation of histone H2AX after heating. J Radiat Res. 2008;51:417–22.

    Article  Google Scholar 

  49. Takahashi A, Mori E, Ohnishi T. The foci of DNA double strand break-recognition proteins localize with γH2AX after heat treatment. J Radiat Res. 2010;51:91–5.

    Article  CAS  PubMed  Google Scholar 

  50. Hunt CR, Pandita RK, Laszlo A, Higashikubo R, Agarwal M, Kitamura T, et al. Hyperthermia activates a subset of ataxia-telangiectasia mutated effectors independent of DNA strand breaks and heat shock protein 70 status. Cancer Res. 2007;67:3010–17.

    Article  CAS  PubMed  Google Scholar 

  51. Laszlo A, Fleischer I. The heat-induced γ-H2AX response does not play a role in hyperthermic cell killing. Int J Hyperthermia. 2009;25:199–209.

    Article  CAS  PubMed  Google Scholar 

  52. Laszlo A, Fleischer I. Heat-induced perturbations of DNA damage signaling pathways are modulated by molecular chaperones. Cancer Res. 2009;69:2042–9.

    Article  CAS  PubMed  Google Scholar 

  53. Kampinga HH, Laszlo A. DNA double strand breaks do not play a role in heat-induced cell killing. Cancer Res. 2005;65:10632–3.

    Article  CAS  PubMed  Google Scholar 

  54. Zhu WG, Seno JD, Beck BD, Dynlacht JR. Translocation of MRE11 from the nucleus to the cytoplasm as a mechanism of radiosensitization by heat. Radiat Res. 2001;156:95–102.

    Article  CAS  PubMed  Google Scholar 

  55. Seno JD, Dynlacht JR. Intracellular redistribution and modification of proteins of the Mre11/Rad50/Nbs1 DNA repair complex following irradiation and heat-shock. J Cell Physiol. 2004;199:157–70.

    Article  CAS  PubMed  Google Scholar 

  56. Xu M, Myerson RJ, Xia Y, Whitehead T, Moros EG, Straube WL, et al. The effects of 41 degrees C hyperthermia on the DNA repair protein, MRE11, correlate with radiosensitization in four human tumor cell lines. Int J Hyperthermia. 2007;23:343–51.

    Article  CAS  PubMed  Google Scholar 

  57. Gerashchenko BI, Gooding G, Dynlacht JR. Hyperthermia alters the interaction of proteins of the Mre11 complex in irradiated cells. Cytometry A. 2010;77:940–52.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Miyakoda M, Suzuki K, Kodama S, Watanabe M. Activation of ATM and phosphorylation of p53 by heat shock. Oncogene. 2002;21:1090–6.

    Article  CAS  PubMed  Google Scholar 

  59. Genet SC, Fujii Y, Maeda J, Kaneko M, Genet MD, Miyagawa K, et al. Hyperthermia inhibits homologous recombination repair and sensitizes cells to ionizing radiation in a time- and temperature-dependent manner. J Cell Physiol. 2013;228:1473–81.

    Article  CAS  PubMed  Google Scholar 

  60. Inoue K, Kawata T, Saito M, Liu C, Uno T, Isobe K, et al. Effect of an ATM kinase inhibitor on thermo- and/or radio-sensitization in non-proliferating normal human fibroblasts and osteosarcoma cells. Thermal Med. 2010;26:97–107.

    Article  Google Scholar 

  61. Takahashi A, Mori E, Ohnishi T. A possible role of DNA double strand breaks in heat-induced cell killing. Cancer Res. 2005;65:10633.

    Google Scholar 

  62. van der Waal RP, Griffith CL, Wright WD, Borrelli MJ, Roti Roti JL. Delaying S-phase progression rescues cells from heat-induced S-phase hypertoxicity. J Cell Physiol. 2001;187:236–43.

    Article  Google Scholar 

  63. Lukas C, Savic V, Bekker-Jensen S, Doil C, Neumann B, Pedersen RS, et al. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress. Nat Cell Biol. 2011;13:243–53.

    Article  CAS  PubMed  Google Scholar 

  64. Westra A, Dewey WC. Variation in sensitivity to heat shock during the cell-cycle of Chinese hamster cells in vitro. Int J Radiat Biol. 1971;19:467–77.

    CAS  Google Scholar 

  65. Takahashi A, Ohnishi T. What is the critical hyperthermia target in cancer cells? Thermal Med. 2006;22:229–37.

    Article  Google Scholar 

  66. Mori E, Takahashi A, Ohnishi T. The biology of heat-induced DNA double-strand breaks. Thermal Med. 2008;24:39–50.

    Article  Google Scholar 

  67. Kenny MK, Mendez F, Sandigursky M, Kureekattil RP, Goldman JD, Franklin WA, et al. Heat shock protein 70 binds to human apurinic/apyrimidinic endonuclease and stimulates endonuclease activity at abasic sites. J Biol Chem. 2001;276:9532–6.

    Article  CAS  PubMed  Google Scholar 

  68. Spiro IJ, Denman DL, Dewey WC. Effect of hyperthermia on CHO DNA polymerases alpha and beta. Radiat Res. 1982;89:134–49.

    Article  CAS  PubMed  Google Scholar 

  69. Jorritsma JB, Kampinga HH, Scaf AH, Konings AW. Strand break repair, DNA polymerase activity and heat radiosensitization in thermotolerant cells. Int J Hyperthermia. 1985;1:131–45.

    Article  CAS  PubMed  Google Scholar 

  70. Mivechi NF, Miyachi H, Scanlon KJ. Heat radiosensitization and the level of DNA polymerases alpha and beta of human colony-forming unit-granulocyte-macrophage and myeloid leukemias sensitive and resistant to chemotherapeutic agents. Cancer Res. 1990;50:2044–8.

    CAS  PubMed  Google Scholar 

  71. Sobol RW, Horton JK, Kühn R, Gu H, Singhal RK, Prasad R, et al. Requirement of mammalian DNA polymerase-βin base-excision repair. Nature. 1996;379:183–6.

    Article  CAS  PubMed  Google Scholar 

  72. Sobol RW, Prasad R, Evenski A, Baker A, Yang XP, Horton JK, et al. The lyase activity of the DNA repair protein β-polymerase protects from DNA-damage-induced cytotoxicity. Nature. 2000;405:807–10.

    Article  CAS  PubMed  Google Scholar 

  73. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–17.

    Article  CAS  PubMed  Google Scholar 

  74. Hall EJ, Giaccia AJ. Radiobiology for the radiologist. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2012.

    Google Scholar 

  75. Wouters BG, Begg AC. Irradiation-induced damage and the DNA damage response. In: Joiner M, van der Kogel A, editors. Basic clinical radiobiology. 4th ed. London: Hodder Arnold Publication; 2009. p. 11–26.

    Chapter  Google Scholar 

  76. Shibata A, Conrad S, Birraux J, Geuting V, Barton O, Ismail A, et al. Factors determining DNA double-strand break repair pathway choice in G2 phase. EMBO J. 2011;30:1079–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Terato H, Tanaka R, Nakaarai Y, Nohara T, Doi Y, Iwai S, et al. Quantitative analysis of isolated and clustered DNA damage induced by gamma-rays, carbon ion beams, and iron ion beams. J Radiat Res. 2008;49:133–46.

    Article  CAS  PubMed  Google Scholar 

  78. Burgman P, Ouyang H, Peterson S, Chen DJ, Li GC. Heat inactivation of Ku autoantigen: possible role in hyperthermic radiosensitization. Cancer Res. 1997;57:2847–50.

    CAS  PubMed  Google Scholar 

  79. Matsumoto Y, Suzuki N, Sakai K, Morimatsu A, Hirano K, Murofushi H. A possible mechanism for hyperthermic radiosensitization mediated through hyperthermic lability of Ku subunits in DNA-dependent protein kinase. Biochem Biophys Res Commun. 1997;234:568–72.

    Article  CAS  PubMed  Google Scholar 

  80. Ihara M, Suwa A, Komatsu K, Shimasaki T, Okaichi K, Hendrickson EA, et al. Heat sensitivity of double-stranded DNA-dependent protein kinase (DNA-PK) activity. Int J Radiat Biol. 1999;75:253–8.

    Article  CAS  PubMed  Google Scholar 

  81. Beck BD, Dynlacht JR. Heat-induced aggregation of XRCC5 (Ku80) in nontolerant and thermotolerant cells. Radiat Res. 2001;156:767–74.

    Article  CAS  PubMed  Google Scholar 

  82. Ihara M, Takeshita S, Okaichi K, Okumura Y, Ohnishi T. Heat exposure enhances radiosensitivity by depressing DNA-PK kinase activity during double strand break repair. Int J Hyperthermia. 2014;30:102–9.

    Article  CAS  PubMed  Google Scholar 

  83. Krawczyk PM, Eppink B, Essers J, Stap J, Rodermond H, Odijk H, et al. Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly(ADP-ribose) polymerase-1 inhibition. Proc Natl Acad Sci U S A. 2011;108:9851–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Jeggo PA, Geuting V, Löbrich M. The role of homologous recombination in radiation-induced double-strand break repair. Radiother Oncol. 2011;101:7–12.

    Article  CAS  PubMed  Google Scholar 

  85. Lindahl T. Instability and decay of the primary structure of DNA. Nature. 1993;362:709–15.

    Article  CAS  PubMed  Google Scholar 

  86. Vilenchik MM, Knudson AG. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci U S A. 2003;100:12871–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Gunma University Heavy Ion Medical Center, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Akihisa Takahashi

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  1. Kokura Lab, Health and Medical Sciences, Kyoto Gakuen University, Kyoto, Kyoto, Japan

    Satoshi Kokura

  2. Department of Inflammation and Immunolog, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan

    Toshikazu Yoshikawa

  3. Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan

    Takeo Ohnishi

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Takahashi, A. (2016). Molecular Damage: Hyperthermia Alone. In: Kokura, S., Yoshikawa, T., Ohnishi, T. (eds) Hyperthermic Oncology from Bench to Bedside. Springer, Singapore. https://doi.org/10.1007/978-981-10-0719-4_3

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