Skip to main content

Experimental Models for Ionizing Radiation Research

  • Chapter
  • First Online:
  • 1240 Accesses

Abstract

Ionizing radiation is a valuable tool used for cancer treatment as well as for basic molecular research. More recent interest stems from a need to provide countermeasures against accidental or intentional exposure to radiation through nuclear devices. This chapter provides an overview of the biological effects of radiation and highlights models used to study radiation-induced damage and repair. In vitro and in vivo endpoints including DNA damage, cell survival, apoptosis, cytogenetic aberrations, oxidative stress, tumor response, and genomic instability are discussed. Appropriate use of these models will facilitate the advancement of radiation research as novel molecular mechanisms are elucidated.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ATM:

Ataxia telangectasia mutant

AZD:

Astrazeneca Chk1 inhibitor

Bcl-2:

B-cell lymphoma 2

BRCA1/2:

Breast cancer associated 1/2

BSE:

Bystander effect

BUdR:

Bromodeoxyuridine

Chk1/2:

Checkpoint kinase 1/2

CHO:

Chinese hamster ovary cell line

CMXRos:

Chloromethyl-X-rosamine

DCF:

2′,7′-Dichlorofluorescein

DHE:

5-Ethyl-5,6-dihydro-6-phenyl-3,8-diaminophenanthridine, hydroethidine

DiOC6:

3,3′-Dihexyloxacarbocyanine iodide

DMF:

Dose modifying factor

DNA-PKcs:

DNA-dependent protein kinase catalytic subunit

DSB:

Double-strand break

EGFR:

Epidermal growth factor receptor

ELISA:

Enzyme-linked immunosorbent assay

FPG:

Fluorescence plus Giemsa

FX:

Fractionated IR

GI:

Genomic instability

Gy:

Gray

H2AX:

Histone H2A

H2DCF-DA:

2′,7′-Dihydrodichlorofluorescein

HDAC:

Histone deactetylase

HGPRT:

Hypoxanthine–guanine phosphoribosyltransferase

HPLC:

High performance liquid chromatography

HR:

Homologous recombination

Hsp-90:

Heat-shock protein 90

IR:

Ionizing radiation

IUdR:

Iododeoxyurdine

LC3:

Microtubule-associated protein 1 light chain 3

LD50/30 :

Lethal dose for 50% at 30 days

LET:

Linear energy transfer

MN:

Micronuclei

MRN:

Mre11–Rad50–Nbs1

mTor:

Mammalian target of rapamycin

MTS:

3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

MTT:

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide

NFκB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NHEJ:

Nonhomologous end-joining

PARP-1:

Poly (ADP-ribose) polymerase-1

PF:

Protector factor

PFGE:

Pulse field gel electrophoresis

PI3K:

Phosphoinositide 3-kinases

PT:

Permeability transition pores

ROS:

Reactive oxygen species

RPA:

Replication protein A

SCE:

Sister chromatid exchange

SNP:

Single nucleotide polymorphism

SSB:

Single strand break

ssDNA:

Single strand DNA

TCD50 :

Tumor control dose for 50%

TMRE:

Tetramethylrhodamine

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

VEGF:

Vascular endothelial growth factor

XIAP:

X-linked Inhibitor of apoptosis protein

XRCC4:

X-ray repair complementing defective repair in CHO 4

XTT:

2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide

γH2AX:

Gamma (phosphorylated) H2AX

Δy  m:

Membrane potential difference

References

  1. Hall, E.J. and A.J. Giaccia, Radiobiology for the Radiologist. 6th ed. 2006, Philadelphia: Lippincott Williams & Wilkins.

    Google Scholar 

  2. Steel, G.G., Basic Clinincal Radiobiology. 3rd ed. 2002, New York: Hodder Arnold.

    Google Scholar 

  3. von-Sonntag, C., The Chemical Basis of Radiation Biology. 1987, Philadelphia: Taylor & Francis.

    Google Scholar 

  4. Munro, T.R., The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts. Radiat Res, 1970. 42(3): p. 451–  70.

    Article  PubMed  CAS  Google Scholar 

  5. Ward, J.F., DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability. Prog Nucleic Acid Res Mol Biol, 1988. 35:p. 95–125.

    Article  PubMed  CAS  Google Scholar 

  6. Cornforth, M.N. and J.S. Bedford, A quantitative comparison of potentially lethal damage repair and the rejoining of interphase chromosome breaks in low passage normal human fibroblasts. Radiat Res, 1987. 111(3): p. 385–405.

    Article  PubMed  CAS  Google Scholar 

  7. Pfeiffer, P., et al., DNA lesions and repair. Mutat Res, 1996. 366(2): p. 69–80.

    Article  CAS  Google Scholar 

  8. Duggan, D.E., A.W. Anderson, and P.R. Elliker, Inactivation of the Radiation-Resistant Spoilage Bacterium Micrococcus Radiodurans. Ii. Radiation Inactivation Rates as Influenced by Menstruum Temperature, Preirradiation Heat Treatment, and Certain Reducing Agents. Appl Microbiol, 1963. 11: p. 413–7.

    PubMed  CAS  Google Scholar 

  9. Blasius, M., S. Sommer, and U. Hubscher, Deinococcus radiodurans: what belongs to the survival kit? Crit Rev Biochem Mol Biol, 2008. 43(3): p. 221–38.

    Article  PubMed  CAS  Google Scholar 

  10. Pass, H.I., et al., Lung Cancer: Principles and Practice. 2nd ed. 2000, Philadelphia, PA: Lippencott Williams & Wilkins.

    Google Scholar 

  11. Savage, J.R., Update on target theory as applied to chromosomal aberrations. Environ Mol Mutagen, 1993. 22(4): p. 198–207.

    Article  PubMed  CAS  Google Scholar 

  12. Minton, K.W., DNA repair in the extremely radioresistant bacterium Deinococcus radiodurans. Mol Microbiol, 1994. 13(1): p. 9–15.

    Article  PubMed  CAS  Google Scholar 

  13. Brown, J.M. and L.D. Attardi, The role of apoptosis in cancer development and treatment response. Nat Rev Cancer, 2005. 5(3): p. 231–7.

    Article  PubMed  CAS  Google Scholar 

  14. Puck, T.T. and P.I. Marcus, Action of x-rays on mammalian cells. J Exp Med, 1956. 103(5): p. 653–66.

    Article  PubMed  CAS  Google Scholar 

  15. Puck, T.T. and P.I. Marcus, A Rapid Method for Viable Cell Titration and Clone Production with Hela Cells in Tissue Culture: The Use of X-Irradiated Cells to Supply Conditioning Factors. Proc Natl Acad Sci USA, 1955. 41(7): p. 432–7.

    Article  PubMed  CAS  Google Scholar 

  16. Albright, N., Computer programs for the analysis of cellular survival data. Radiat Res, 1987. 112(2): p. 331–40.

    Article  PubMed  CAS  Google Scholar 

  17. Hahn, S.M., et al., Identification of nitroxide radioprotectors. Radiat Res, 1992. 132(1): p. 87–93.

    Article  CAS  Google Scholar 

  18. Thotala, D.K., et al., A new class of molecular targeted radioprotectors: GSK-3beta inhibitors. Int J Radiat Oncol Biol Phys, 2010. 76(2): p. 557–65.

    Article  PubMed  CAS  Google Scholar 

  19. Mitchell, J.B., et al., Differing sensitivity to fluorescent light in Chinese hamster cells containing equally incorporated quantities of BUdR versus IUdR. Int J Radiat Oncol Biol Phys, 1984. 10(8): p. 1447–51.

    Article  PubMed  CAS  Google Scholar 

  20. Kerr, J.F., History of the events leading to the formulation of the apoptosis concept. Toxicology, 2002. 181–182: p. 471–4.

    Article  PubMed  Google Scholar 

  21. Castedo, M., et al., Quantitation of mitochondrial alterations associated with apoptosis. J Immunol Methods, 2002. 265(1-2): p. 39–47.

    Article  PubMed  CAS  Google Scholar 

  22. Huerta, S., et al., Screening and detection of apoptosis. J Surg Res, 2007. 139(1):p. 143–56.

    Article  PubMed  CAS  Google Scholar 

  23. Brown, J.M. and B.G. Wouters, Apoptosis, p53, and tumor cell sensitivity to anticancer agents. Cancer Res, 1999. 59(7): p. 1391–9.

    PubMed  CAS  Google Scholar 

  24. Brown, J.M. and G. Wilson, Apoptosis genes and resistance to cancer therapy: what does the experimental and clinical data tell us? Cancer Biol Ther, 2003. 2(5): p. 477–90.

    PubMed  CAS  Google Scholar 

  25. Dewey, W.C., C.C. Ling, and R.E. Meyn, Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys, 1995. 33(4): p. 781–96.

    Article  PubMed  CAS  Google Scholar 

  26. Verheij, M., Clinical biomarkers and imaging for radiotherapy-induced cell death. Cancer Metastasis Rev, 2008. 27(3): p. 471–80.

    Article  PubMed  Google Scholar 

  27. Hotchkiss, R.S., et al., Cell death. N Engl J Med, 2009. 361(16): p. 1570–83.

    Article  CAS  Google Scholar 

  28. Yang, Z. and D.J. Klionsky, An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol, 2009. 335: p. 1–32.

    Article  PubMed  CAS  Google Scholar 

  29. Nelson, D.A. and E. White, Exploiting different ways to die. Genes Dev, 2004. 18(11): p. 1223–6.

    Article  PubMed  CAS  Google Scholar 

  30. White, E. and R.S. DiPaola, The double-edged sword of autophagy modulation in cancer. Clin Cancer Res, 2009. 15(17): p. 5308–16.

    Article  PubMed  Google Scholar 

  31. Kroemer, G. and E. White, Autophagy for the avoidance of degenerative, inflammatory, infectious, and neoplastic disease. Curr Opin Cell Biol, 2010. 22(2): p. 121–3.

    Article  PubMed  CAS  Google Scholar 

  32. Barth, S., D. Glick, and K.F. Macleod, Autophagy: assays and artifacts. J Pathol, 2010.

    Google Scholar 

  33. Komatsu, M., et al., Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell, 2007. 131(6): p. 1149–63.

    Article  PubMed  CAS  Google Scholar 

  34. Jin, S., et al., Metabolic catastrophe as a means to cancer cell death. J Cell Sci, 2007. 120(Pt 3): p. 379–83.

    Article  PubMed  CAS  Google Scholar 

  35. Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 1983. 65(1-2): p. 55–63.

    Article  PubMed  CAS  Google Scholar 

  36. Marshall, N.J., C.J. Goodwin, and S.J. Holt, A critical assessment of the use of microculture tetrazolium assays to measure cell growth and function. Growth Regul, 1995. 5(2): p. 69–84.

    PubMed  CAS  Google Scholar 

  37. Carmichael, J., et al., Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res, 1987. 47(4): p. 936–42.

    PubMed  CAS  Google Scholar 

  38. Carmichael, J., et al., Chemosensitivity testing of human lung cancer cell lines using the MTT assay. Br J Cancer, 1988. 57(6): p. 540–7.

    Article  PubMed  CAS  Google Scholar 

  39. Carmichael, J., et al., Radiation sensitivity of human lung cancer cell lines. Eur J Cancer Clin Oncol, 1989. 25(3): p. 527–34.

    Article  PubMed  CAS  Google Scholar 

  40. Ishikawa, K., H. Ishii, and T. Saito, DNA damage-dependent cell cycle checkpoints and genomic stability. DNA Cell Biol, 2006. 25(7): p. 406–11.

    Article  PubMed  CAS  Google Scholar 

  41. Sancar, A., et al., Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem, 2004. 73: p. 39–85.

    Article  PubMed  CAS  Google Scholar 

  42. Hartlerode, A.J. and R. Scully, Mechanisms of double-strand break repair in somatic mammalian cells. Biochem J, 2009. 423(2): p. 157–68.

    Article  PubMed  CAS  Google Scholar 

  43. Ma, Y., et al., Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell, 2002. 108(6): p. 781–94.

    Article  PubMed  CAS  Google Scholar 

  44. Buck, D., et al., Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell, 2006. 124(2): p. 287–99.

    Article  PubMed  CAS  Google Scholar 

  45. Hanakahi, L.A., et al., Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair. Cell, 2000. 102(6): p. 721–9.

    Article  PubMed  CAS  Google Scholar 

  46. Block, W.D., et al., Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit regulates ligation of DNA ends. Nucleic Acids Res, 2004. 32(14): p. 4351–7.

    Article  PubMed  CAS  Google Scholar 

  47. Auckley, D.H., et al., Reduced DNA-dependent protein kinase activity is associated with lung cancer. Carcinogenesis, 2001. 22(5): p. 723–7.

    Article  PubMed  CAS  Google Scholar 

  48. Lavin, M.F., Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol, 2008. 9(10): p. 759–69.

    Article  PubMed  CAS  Google Scholar 

  49. Han, J., et al., Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses’ Health Study. Carcinogenesis, 2004. 25(2): p. 189–95.

    Article  PubMed  CAS  Google Scholar 

  50. Kuschel, B., et al., Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet, 2002. 11(12): p. 1399–407.

    Article  PubMed  CAS  Google Scholar 

  51. Rafii, S., et al., A potential role for the XRCC2 R188H polymorphic site in DNA-damage repair and breast cancer. Hum Mol Genet, 2002. 11(12): p. 1433–8.

    Article  PubMed  CAS  Google Scholar 

  52. Roddam, P.L., et al., Genetic variants of NHEJ DNA ligase IV can affect the risk of developing multiple myeloma, a tumour characterised by aberrant class switch recombination. J Med Genet, 2002. 39(12): p. 900–5.

    Article  PubMed  CAS  Google Scholar 

  53. Bhatti, P., et al., Polymorphisms in DNA repair genes, ionizing radiation exposure and risk of breast cancer in U.S. Radiologic technologists. Int J Cancer, 2008. 122(1): p. 177–  82.

    Google Scholar 

  54. Helleday, T., Pathways for mitotic homologous recombination in mammalian cells. Mutat Res, 2003. 532(1-2): p. 103–15.

    PubMed  CAS  Google Scholar 

  55. Jeggo, P. and M.F. Lavin, Cellular radiosensitivity: how much better do we understand it? Int J Radiat Biol, 2009. 85(12): p. 1061–81.

    Article  PubMed  CAS  Google Scholar 

  56. Venkitaraman, A.R., Functions of BRCA1 and BRCA2 in the biological response to DNA damage. J Cell Sci, 2001. 114(Pt 20): p. 3591–8.

    PubMed  CAS  Google Scholar 

  57. Wenham, R.M., et al., Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer. Clin Cancer Res, 2003. 9(12): p. 4396–403.

    PubMed  CAS  Google Scholar 

  58. Elkind, M.M. and C. Kamper, Two forms of repair of DNA in mammalian cells following irradiation. Biophys J, 1970. 10(3): p. 237–45.

    Article  PubMed  CAS  Google Scholar 

  59. Zwelling, L.A., et al., Protein-associated deoxyribonucleic acid strand breaks in L1210 cells treated with the deoxyribonucleic acid intercalating agents 4-(9-acridinylamino) methanesulfon-m-anisidide and adriamycin. Biochemistry, 1981. 20(23): p. 6553–63.

    Article  PubMed  CAS  Google Scholar 

  60. Geigl, E.M. and F. Eckardt-Schupp, The repair of double-strand breaks and S1 nuclease-sensitive sites can be monitored chromosome-specifically in Saccharomyces cerevisiae using pulse-field gel electrophoresis. Mol Microbiol, 1991. 5(7): p. 1615–20.

    Article  PubMed  CAS  Google Scholar 

  61. Okayasu, R., et al., A deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c mouse. Cancer Res, 2000. 60(16): p. 4342–5.

    PubMed  CAS  Google Scholar 

  62. Stamato, T.D. and N. Denko, Asymmetric field inversion gel electrophoresis: a new method for detecting DNA double-strand breaks in mammalian cells. Radiat Res, 1990. 121(2):p. 196–205.

    Article  PubMed  CAS  Google Scholar 

  63. Olive, P.L., Impact of the comet assay in radiobiology. Mutat Res, 2009. 681(1): p. 13–23.

    Article  PubMed  CAS  Google Scholar 

  64. Olive, P.L., J.P. Banath, and R.E. Durand, Detection of etoposide resistance by measuring DNA damage in individual Chinese hamster cells. J Natl Cancer Inst, 1990. 82(9): p. 779–83.

    Article  PubMed  CAS  Google Scholar 

  65. Pilch, D.R., et al., Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol, 2003. 81(3): p. 123–9.

    Article  PubMed  CAS  Google Scholar 

  66. Rogakou, E.P., et al., DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem, 1998. 273(10): p. 5858–68.

    Article  PubMed  CAS  Google Scholar 

  67. Mitchell, J.B., et al., In vitro and in vivo radiation sensitization of human tumor cells by a novel checkpoint kinase inhibitor, AZD7762. Clin Cancer Res, 2010. 16(7): p. 2076–84.

    Article  PubMed  CAS  Google Scholar 

  68. Banath, J.P., et al., Explanation for excessive DNA single-strand breaks and endogenous repair foci in pluripotent mouse embryonic stem cells. Exp Cell Res, 2009. 315(8):p. 1505–20.

    Article  PubMed  CAS  Google Scholar 

  69. Kinner, A., et al., Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res, 2008. 36(17): p. 5678–94.

    Article  PubMed  CAS  Google Scholar 

  70. Rothkamm, K. and S. Horn, gamma-H2AX as protein biomarker for radiation exposure. Ann Ist Super Sanita, 2009. 45(3): p. 265–71.

    PubMed  CAS  Google Scholar 

  71. Smith, L.E., et al., Radiation-induced genomic instability: radiation quality and dose response. Health Phys, 2003. 85(1): p. 23–9.

    Article  PubMed  CAS  Google Scholar 

  72. Morgan, W.F., Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation? Oncogene, 2003. 22(45): p. 7094–9.

    Article  PubMed  CAS  Google Scholar 

  73. Little, J.B., Lauriston S. Taylor lecture: nontargeted effects of radiation: implications for low-dose exposures. Health Phys, 2006. 91(5): p. 416–26.

    Article  PubMed  CAS  Google Scholar 

  74. Morgan, W.F., Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects. Radiat Res, 2003. 159(5): p. 581–96.

    Article  PubMed  CAS  Google Scholar 

  75. Hei, T.K., et al., Advances in radiobiological studies using a microbeam. J Radiat Res (Tokyo), 2009. 50 Suppl A: p. A7–A12.

    Google Scholar 

  76. Nagasawa, H. and J.B. Little, Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res, 1992. 52(22): p. 6394–6.

    PubMed  CAS  Google Scholar 

  77. Mothersill, C. and C. Seymour, Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells. Int J Radiat Biol, 1997. 71(4): p. 421–7.

    Article  PubMed  CAS  Google Scholar 

  78. Hagelstrom, R.T., et al., DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals. Oncogene, 2008. 27(53): p. 6761–9.

    Article  PubMed  CAS  Google Scholar 

  79. Harada, T., et al., Different involvement of radical species in irradiated and bystander cells. Int J Radiat Biol, 2008. 84(10): p. 809–14.

    Article  PubMed  CAS  Google Scholar 

  80. Ponnaiya, B., M.N. Cornforth, and R.L. Ullrich, Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white. Radiat Res, 1997. 147(2): p. 121–5.

    Article  PubMed  CAS  Google Scholar 

  81. Perry, P. and S. Wolff, New Giemsa method for the differential staining of sister chromatids. Nature, 1974. 251(5471): p. 156–8.

    Article  PubMed  CAS  Google Scholar 

  82. Fenech, M., The in vitro micronucleus technique. Mutat Res, 2000. 455(1-2): p. 81–95.

    PubMed  CAS  Google Scholar 

  83. Han, W., et al., Nitric oxide mediated DNA double strand breaks induced in proliferating bystander cells after alpha-particle irradiation. Mutat Res, 2010. 684(1-2): p. 81–9.

    PubMed  CAS  Google Scholar 

  84. Bailey, S.M. and J.S. Bedford, Studies on chromosome aberration induction: what can they tell us about DNA repair? DNA Repair (Amst), 2006. 5(9-10): p. 1171–81.

    Google Scholar 

  85. 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(1): p. 75–97.

    CAS  Google Scholar 

  86. Zhou, H., et al., Quantification of CD59- mutants in human-hamster hybrid (AL) cells by flow cytometry. Mutat Res, 2006. 594(1-2): p. 113–9.

    PubMed  CAS  Google Scholar 

  87. Little, J.B., et al., Bystander effects: intercellular transmission of radiation damage signals. Radiat Prot Dosimetry, 2002. 99(1-4): p. 159–62.

    Article  PubMed  CAS  Google Scholar 

  88. Nagasawa, H. and J.B. Little, Unexpected sensitivity to the induction of mutations by very low doses of alpha-particle radiation: evidence for a bystander effect. Radiat Res, 1999. 152(5): p. 552–7.

    Article  PubMed  CAS  Google Scholar 

  89. Kinashi, Y., et al., Bystander effect-induced mutagenicity in HPRT locus of CHO cells following BNCT neutron irradiation: characteristics of point mutations by sequence analysis. Appl Radiat Isot, 2009. 67(7-8 Suppl): p. S325–7.

    Article  PubMed  CAS  Google Scholar 

  90. Waldren, C., C. Jones, and T.T. Puck, Measurement of mutagenesis in mammalian cells. Proc Natl Acad Sci U S A, 1979. 76(3): p. 1358  –  62.

    Article  PubMed  CAS  Google Scholar 

  91. Jones, C., P. Wuthier, and T.T. Puck, Genetics of somatic cell surface antigens. III. Further analysis of the AL marker. Somatic Cell Genet, 1975. 1(3): p. 235–46.

    Article  CAS  Google Scholar 

  92. Puck, T.T., et al., Genetics of somatic mammalian cells: lethal antigens as genetic markers for study of human linkage groups. Proc Natl Acad Sci USA, 1971. 68(12): p. 3102–6.

    Article  PubMed  CAS  Google Scholar 

  93. Persaud, R., et al., Assessment of low linear energy transfer radiation-induced bystander mutagenesis in a three-dimensional culture model. Cancer Res, 2005. 65(21): p. 9876–82.

    Article  PubMed  CAS  Google Scholar 

  94. Wu, L.J., et al., Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells. Proc Natl Acad Sci USA, 1999. 96(9): p. 4959–64.

    Article  PubMed  CAS  Google Scholar 

  95. Hei, T.K., et al., Mutagenic effects of a single and an exact number of alpha particles in mammalian cells. Proc Natl Acad Sci USA, 1997. 94(8): p. 3765–70.

    Article  PubMed  CAS  Google Scholar 

  96. Zielonka, J. and B. Kalyanaraman, Hydroethidine- and MitoSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: another inconvenient truth. Free Radic Biol Med, 2010. 48(8): p. 983–1001.

    Article  PubMed  CAS  Google Scholar 

  97. Zhao, H., et al., Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence. Proc Natl Acad Sci USA, 2005. 102(16): p. 5727–32.

    Article  PubMed  CAS  Google Scholar 

  98. Stone, H.B., et al., Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol, 2003. 4(9): p. 529–36.

    Article  PubMed  CAS  Google Scholar 

  99. Stone, H.B., W.H. McBride, and C.N. Coleman, Modifying normal tissue damage postirradiation. Report of a workshop sponsored by the Radiation Research Program, National Cancer Institute, Bethesda, Maryland, September 6-8, 2000. Radiat Res, 2002. 157(2): p. 204  –23.

    Article  PubMed  CAS  Google Scholar 

  100. Dutreix, J., M. Tubiana, and A. Dutreix, An approach to the interpretation of clinical data on the tumour control probability-dose relationship. Radiother Oncol, 1988. 11(3): p. 239–48.

    Article  PubMed  CAS  Google Scholar 

  101. McNally, N.J. and P.W. Sheldon, The effect of radiation on tumour growth delay, cell survival and cure of the animal using a single tumour system. Br J Radiol, 1977. 50(593): p. 321–8.

    Article  PubMed  CAS  Google Scholar 

  102. Hahn, S.M., et al., Evaluation of tempol radioprotection in a murine tumor model. Free Radic Biol Med, 1997. 22(7): p. 1211–6.

    Article  PubMed  CAS  Google Scholar 

  103. Ellington, O.B., Cis-platinum: a brief review of its use, and nursing guidelines. Cancer Nurs, 1978. 1(5): p. 403–6.

    PubMed  CAS  Google Scholar 

  104. Evseenko, L.S., et al., [5-fluorouracil in the chemotherapy of malignant neoplasms]. Vopr Onkol, 1966. 12(1): p. 92–106.

    PubMed  CAS  Google Scholar 

  105. Erlichman, C., Novel chemotherapeutic agents in clinical development. Curr Opin Oncol, 1991. 3(6): p. 1037–42.

    Article  PubMed  CAS  Google Scholar 

  106. Dumont, F., A. Altmeyer, and P. Bischoff, Radiosensitising agents for the radiotherapy of cancer: novel molecularly targeted approaches. Expert Opin Ther Pat, 2009. 19(6):p. 775–99.

    Article  PubMed  CAS  Google Scholar 

  107. Sarkaria, J.N. and J.S. Eshleman, ATM as a target for novel radiosensitizers. Semin Radiat Oncol, 2001. 11(4): p. 316–27.

    Article  PubMed  CAS  Google Scholar 

  108. Ortiz, T., et al., Radiosensitizer effect of wortmannin in radioresistant bladder tumoral cell lines. Int J Oncol, 2004. 24(1): p. 169–75.

    PubMed  CAS  Google Scholar 

  109. Khan, K., et al., Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427. Head Neck, 2010. 32(3): p. 381–91.

    PubMed  Google Scholar 

  110. Janetka, J.W., et al., Inhibitors of checkpoint kinases: from discovery to the clinic. Curr Opin Drug Discov Devel, 2007. 10(4): p. 473–86.

    PubMed  CAS  Google Scholar 

  111. Harari, P.M. and S. Huang, Radiation combined with EGFR signal inhibitors: head and neck cancer focus. Semin Radiat Oncol, 2006. 16(1): p. 38–  44.

    Article  PubMed  Google Scholar 

  112. Prevo, R., et al., Class I PI3 kinase inhibition by the pyridinylfuranopyrimidine inhibitor PI-103 enhances tumor radiosensitivity. Cancer Res, 2008. 68(14): p. 5915–23.

    Article  PubMed  CAS  Google Scholar 

  113. Diaz, R., et al., The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer. Br J Cancer, 2009. 100(6): p. 932–  40.

    Article  PubMed  CAS  Google Scholar 

  114. Ahmed, K.M. and J.J. Li, NF-kappa B-mediated adaptive resistance to ionizing radiation. Free Radic Biol Med, 2008. 44(1): p. 1–13.

    Article  PubMed  CAS  Google Scholar 

  115. Capalbo, G., et al., The role of survivin for radiation therapy. Prognostic and predictive factor and therapeutic target. Strahlenther Onkol, 2007. 183(11): p. 593–9.

    Article  Google Scholar 

  116. Bristow, R.G., S. Benchimol, and R.P. Hill, The p53 gene as a modifier of intrinsic radiosensitivity: implications for radiotherapy. Radiother Oncol, 1996. 40(3): p. 197–223.

    Article  PubMed  CAS  Google Scholar 

  117. An, J., et al., Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene, 2007. 26(5): p. 652–61.

    Article  PubMed  CAS  Google Scholar 

  118. Karikari, C.A., et al., Targeting the apoptotic machinery in pancreatic cancers using small-molecule antagonists of the X-linked inhibitor of apoptosis protein. Mol Cancer Ther, 2007. 6(3): p. 957–66.

    Article  PubMed  CAS  Google Scholar 

  119. Bozec, A., et al., Combined effects of bevacizumab with erlotinib and irradiation: a preclinical study on a head and neck cancer orthotopic model. Br J Cancer, 2008. 99(1): p. 93–9.

    Article  PubMed  CAS  Google Scholar 

  120. Camphausen, K. and P.J. Tofilon, Inhibition of histone deacetylation: a strategy for tumor radiosensitization. J Clin Oncol, 2007. 25(26): p. 4051–6.

    Article  PubMed  CAS  Google Scholar 

  121. Camphausen, K. and P.J. Tofilon, Inhibition of Hsp90: a multitarget approach to radiosensitization. Clin Cancer Res, 2007. 13(15 Pt 1): p. 4326–30.

    Article  PubMed  CAS  Google Scholar 

  122. Patt, H.M., et al., Cysteine Protection against X Irradiation. Science, 1949. 110(2852): p. 213–214.

    CAS  Google Scholar 

  123. Rasey, J.S., et al., Radioprotection of normal tissues against gamma rays and cyclotron neutrons with WR-2721: LD50 studies and 35S-WR-2721 biodistribution. Radiat Res, 1984. 97(3): p. 598–607.

    Article  PubMed  CAS  Google Scholar 

  124. Spalding, A.C. and T.S. Lawrence, New and emerging radiosensitizers and radioprotectors. Cancer Invest, 2006. 24(4): p. 444–56.

    Article  PubMed  CAS  Google Scholar 

  125. Mitchell, J.B. and M.C. Krishna, Nitroxides as radiation protectors. Mil Med, 2002. 167(2 Suppl): p. 49–50.

    PubMed  Google Scholar 

  126. Stone, H.B., et al., Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI Workshop, December 3-4, 2003. Radiat Res, 2004. 162(6): p. 711–28.

    Article  PubMed  CAS  Google Scholar 

  127. Coleman, C.N., et al., Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda, Maryland, December 17-18, 2001. Radiat Res, 2003. 159(6): p. 812–34.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Murali C. Krishna .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Fabre, K., DeGraff, W., Cook, J.A., Krishna, M.C., Mitchell, J.B. (2011). Experimental Models for Ionizing Radiation Research. In: Basu, S., Wiklund, L. (eds) Studies on Experimental Models. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-956-7_17

Download citation

Publish with us

Policies and ethics