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Cytotechnology

, Volume 12, Issue 1–3, pp 325–345 | Cite as

The biology of radioresistance: similarities, differences and interactions with drug resistance

  • Simon N. Powell
  • Edward H. Abraham
Article

Abstract

Cells and tissues have developed a variety of ways of responding to a hostile environment, be it from drugs (toxins) or radiation (summarized in Fig. 1). Three categories of radiation damage limitation are: (i) DNA repair (ii) changes in cellular metabolism (iii) changes in cell interaction (cell contact or tissue-based resistance; whole organism based resistance).

DNA repair has been evaluated predominantly by the study of repair-deficient mutants. The function of the repair genes they lack is not fully understood, but some of their important interactions are now characterized. For example, the interaction of transcription factors with nucleotide excision repair is made clear by the genetic syndromes of xeroderma-pigmentosum groups B, D and G. These diseases demonstrate ultraviolet light sensitivity and general impairment of transcription: they are linked by impaired unwinding of the DNA required for both transcription and repair. The transfer of DNA into cells is sometimes accompanied by a change in sensitivity to radiation, and this is of special interest when this is the same genetic change seen in tumors. DNA repair has a close relationship with the cell cycle and cell cycle arrest in response to damage may determine sensitivity to that damage. DNA repair mechanisms in response to a variety of drugs and types of radiation can be difficult to study because of the inability to target the damage to defined sequencesin vivo and the lack of a statisfactory substrate forin vitro studies.

Changes in cellular metabolism as a result of ionizing radiation can impart radiation resistance, which is usually transientin vitro, but may be more significantin vivo for tissues or tumors. The mechanisms by which damage is sensed by cells is unknown. The detection of free radicals is thought likely, but distortion to DNA structure or strand breakage and a direct effect on membranes are other possibilities for which there is evidence. Changes in extracellular ATP occur in response to damage, and this could be a direct membrane effect. External purinergic receptors can then be involved in signal transduction pathways resulting in altered levels of thiol protection or triggering apoptosis. Changes in the functional level of proteins as a consequence of ionizing radiation include transcription factors, for example c-jun and c-fos; cell cycle arrest proteins such as GADD (growth arrest and DNA damage inducible proteins) and p53; growth factors such as FGF, PDGF; and other proteins leading to radioresistance. Mechanisms for intercellular resistance could be mediated by cell contact, such as gap junctions, which may help resistance to radiation in non-cycling cells. Paracrine response mechanisms, such as the release of angiogenic factors via membrane transport channels may account for tissue and tumor radiation resistance. Endocrine response mechanisms may also contribute to tissue or tumor resistance.

Key words

cell cycle arrest cell membrane DNA repair oncogene radiation resistance signal transduction 

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References

  1. Abraham EH, Prat AG, Gerweck L, Seneveratne T, Arceci RJ, Kramer R, Guidotti G and Cantiello HF (1993) The multi-drug resistance (mdr1) gene product functions as an ATP channel. Proc Natl Acad Sci USA 90 (1): 312–316.Google Scholar
  2. Biedermann KA, Sun J, Giaccia AJ, Tosto LM and Brown JM (1991) Scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. Proc Natl Acad Sci USA 88: 1394–1397.Google Scholar
  3. Blöcher D and Pohlit W (1982) DNA double-strand breaks in Ehrlich ascites tumour cells at low doses of x-rays. II. Can cell death be attributed to double-strand breaks? Int J Radiat Biol 42: 329–338.Google Scholar
  4. Boeynaems JM, Demolle D, Pirotton S, Raspe E, Lecomte M, Hepburn A, Van Coevorden A and Erneux C (1988) Control of prostacyclin production by vascular cells: role of adenine nucleotides and serotonin. Adv Exp Med Biol 243: 13–20.Google Scholar
  5. Boeynaems JM and Pearson JD (1990) P2 purinoceptors on vascular endothelial cells: physiological significance and transduction mechanisms. Trends Pharmacol Sci 11: 34–37.Google Scholar
  6. Boeynaems JM, Pirotton S, Van Coevorden A, Raspe E, Demolle D and Erneux C (1988) P2-purinergic receptors in vascular endothelial cells: from concept to reality. J Recept Res 8: 121–132.Google Scholar
  7. Bohr VA, Smith CA, Okumoto DS and Hanawalt PC (1985) DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall. Cell 40: 359–369.Google Scholar
  8. Boothman DA, Bouvard I and Hughes EN (1989) Identification and characterization of x-ray-induced proteins in human cells. Cancer Res 49: 2871–2878.Google Scholar
  9. Bootsma D, Koken MHM, van Duin M, Westerwald A, Yasui A, Prakash S and Hoeijmakers JHJ (1987) Homology of mammalian, drosophila, yeast andE. coli repair genes. In: Fielden EM, Fowler JF, Hendry JH and Scott D (eds.) Proceedings of the 8th International Congress of Radiation Research, Edinburgh, July 1987, Taylor and Francis Ltd., London, pp. 412–417.Google Scholar
  10. Bootsma D, Westerveld A and Hoeijmakers JHJ (1988) DNA repair in human cells: from genetic complementation to isolation of genes. Cancer Surveys 7 (2): 303–316.Google Scholar
  11. Bootsma D and Hoeijmakers JHJ (1993) Engagement with transcription. Nature 363: 114–115.Google Scholar
  12. Bradley MO and Kohn KW (1979) x-ray induced DNA double strand break production and repair in mammalian cells as measured by neutral filter elution. Nucleic Acids Res 7: 793–804.Google Scholar
  13. Brunborg G, Resnick MA and Williamson DH (1980) Cell-cycle specific repair of DNA double-strand breaks inSaccharomyces cerevisiae. Radiat Res 82: 547–558.Google Scholar
  14. Burnstock G (1990) Overview: purinergic mechanisms. Ann NY Acad Sci 603: 1–18.Google Scholar
  15. Burt RK, Garfield S, Johnson K, et al. (1988) Transformation of rat liver epithelial cells with v-H-ras or v-raf causes expression of MDR-1, glutathione-S-transferase-P and increased resistant to cytotoxic chemicals. Carcinogenesis 9: 2329–2332.Google Scholar
  16. Chin KV, Ueda K, Pastan I and Gottesman MM (1992) Modulation of activity of the promoter of the human MDR1 gene byRas and p53. Science 255: 459–462.Google Scholar
  17. Debenham PG, Webb MBT, Stretch A and Thacker J (1988a) Examination of vectors with two dominant selectable genes for DNA repair and mutation studies in mammaliancells. Mutat Res 199: 145–158.Google Scholar
  18. Debenham PG, Jones NJ and Webb MBT (1988b) Vector-mediated DNA double-strand break repair analysisin normal, and radiation-sensitive, Chinese hamster V79cells. Mutat Res 199: 1–9.Google Scholar
  19. Defais MJ and Hanawalt PC (1983) Viral probes for DNA repair. Adv Radiat Biol 10: 1–32.Google Scholar
  20. Diller L, Kassel J, Nelson CE, Gryka MA, Litwak G, Gebhardt M, Bressac B, Ozturk M, Baker S, Vogelstein B and Friend SH (1990) p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol 10 (11): 5772–5781.Google Scholar
  21. Downes CS, Musk SR, Watson JV and Johnson RT (1990) Caffeine overcomes a restriction point associated with DNA replication, but does not accelerate mitosis. J Cell Biol 110: 1855–1859.Google Scholar
  22. Durand RE and Sutherland RM (1973) Growth and radiation survival characteristics of V79-171b Chinese hamster cells: a possible influence of intercellular contact. Radiat Res 56: 513–527.Google Scholar
  23. Fairman MP, Johnson AP and Thacker J (1992) Multiple components are involved in the efficient joining of double stranded DNA breaks in human cell. Nucleic Acids Research 20 (16): 4145–4152.Google Scholar
  24. Fields S and Jang SK (1990) Presence of a potent transcription activating sequence in the p53 protein. Science 249: 1046–1049.Google Scholar
  25. Fischer E, Keijzer W, Thielmann HW, Popanda O, Bohnert E, Edler L, Jung EG and Bootsma D (1985) A ninth comple mentation group in xeroderma pigmentosum, XP-I. Mutat Res 145: 217–225.Google Scholar
  26. Fulop GM and Phillips RA (1990) The scid mutation in mice causes a general defect in DNA repair. Nature 347: 479–482.Google Scholar
  27. Fornace AJ, Nebert DW, Hollander MC, Luethy JD, Papathanasiou M, Fargnoli J and Holbrook NJ (1989) Mammalian genes coordinately regulated by growth arrest signals and DNA damaging agents. Mol Cell Biol 9 (10): 4196–4203.Google Scholar
  28. Frankenberg-Schwager M and Frankenberg D (1990) DNA double-strand breaks: their repair and relationship to cell killing in yeast. Int J Radiat Biol 58: 569–575.Google Scholar
  29. Friedberg EC (1985) DNA repair. W.H. Freeman & Co.Google Scholar
  30. Fuks Z and Weichselbaum RR (1992) Radiation tolerance and the new biology: growth factor involvement in radiation injury to the lung. Int J Radiat Oncol Biol Phys 24: 183–184.Google Scholar
  31. Giaccia A, Weinstein R and Stamato TD (1985) Cell-cycle dependent repair of double-strand breaks in a gamma-ray sensitive Chinese hamster ovary cell. Somat Cell Genet 11: 485–491.Google Scholar
  32. Giaccia AJ, Denko N, MacLaren R, Mirman D, Waldren C, Hart I and Stamato TD (1990) Human chromosome 5 complements the DNA double-strand break-repair deficiency and gamma-ray sensitivity of the XR-1 hamster variant. Am J Hum Genet 47: 459–469.Google Scholar
  33. Glazer VM, Glazunov AV, Tevzadze GG and Koltovaia NA (1989) Repair of a double-stranded gap in plasmid DNA in radiosensitive mutants ofSaccharomyces cerevisiae: effectiveness and precision. Mol Gen Mikrobiol Virusol 1989 Sep (9): 14–20.Google Scholar
  34. Goodrich DW, Ping Wang N, Qian YW, Lee EY-HP and Lee WH (1991) The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle. Cell 67: 293–302.Google Scholar
  35. Hallahan DE, Sprigg DR, Beckett MA et al. (1989) Increased tumor necrosis factor mRNA following ionizing radiation exposure. Proc Natl Acad Sci USA 86: 1014–1017.Google Scholar
  36. Hallahan DE, Sukhatme VP, Sherman ML, Virudachalam S, Kufe D and Weichselbaum RR (1991a) Protein kinase C mediates x-ray inducibility of nuclear signal transducers EGR1 and JUN. Proc Natl Acad Sci USA 88: 2156–2160.Google Scholar
  37. Hallahan DE, Virudachalam S, Beckett M, Sherman ML, Kufe D and Weichselbaum RR (1991b) Mechanisms of x-ray-mediated protooncogene c-jun expression in radiation-induced human sarcoma cell lines. Int J Radiat Oncol Biol Phys 21: 1677–1681.Google Scholar
  38. Hallahan DE, Virudachalam S, Schwartz JL, Panje N, Mustati R and Weichselbaum RR (1992) Inhibition of protein kinases sensitizes human tumor cells to ionizing radiation. Radiat Res 129: 345–350.Google Scholar
  39. Hallahan DE, Virudachalam S, Sherman ML, Huberman E, Kufe DW and Weichselbaum RR (1991) Tumor necrosis factor gene expression is mediated by protein kinase C following activation by ionizing radiation. Cancer Res 51: 4565–4569.Google Scholar
  40. Hamilton AA and Thacker J (1987) Gene recombination in x-ray sensitive hamster cells. Mol Cell Biol 7 (4): 1409–1414.Google Scholar
  41. Henderson EE and Long WK (1981) Host cell reactivation of uv and x-ray damaged Herpes simplex virus by Epstein-Barr virus transformed lymphoblastoid cell lines. Virology 115: 237–248.Google Scholar
  42. Hendrickson EA, Qin X-Q, Bump EA, Schatz DG, Oettinger M and Weaver DT (1991) A link between double-strand break-related repair and V(D)J recombination: the scid mutation. Proc Natl Acad Sci USA 88: 4061–4065.Google Scholar
  43. Higgins CF (1992) ABC transporters: from microorganisms to man. Annu Rev Cell Biol 8: 67–113.Google Scholar
  44. Hill BT (1991) Interactions between antitumour agents and radiation and the expression of resistance. Cancer Treat Rev 18: 149–190.Google Scholar
  45. Ho K (1975) Induction of DNA double-strand breaks by x-rays in a radioresistant strain of the yeastSaccharomyces cerevisiae. Mutat Res 30: 327–334.Google Scholar
  46. Hoy CA, Fuscoe JC and Thompson LA (1987) Recombination and ligation of transfected DNA in CHO mutant EM9, which has high levels of sister chromatid exchange. Mol Cell Biol 7 (5): 2007–2011.Google Scholar
  47. Hughes EN and Boothman DA (1991) Effect of caffeine on the expression of a major x-ray induced protein in human tumor cells. Radiat Res 125: 313–317.Google Scholar
  48. Jaspers NGJ, Painter RB, Paterson MC, Kidson C and Inoue T (1985) Complementation analysis of ataxia-telangiectasia. In: Gatti RA and Swift M (eds) Ataxia-telangiectasia: genetics, neuropathology, and immunology of a degenerative disease of childhood. Alan R. Liss, Inc., New York, pp. 147–162.Google Scholar
  49. Jeggo PA (1990) Studies on mammalian mutants defective in rejoining double-strand breaks in DNA. Mutat Res 239 (1): 1–16.Google Scholar
  50. Jeggo PA, Tesmer J and Chen DJ (1991) Genetic analysis of ionising-radiation sensitive mutants of cultured mammalian cell lines. Mutat Res 254: 125–133.Google Scholar
  51. Jones NJ, Cox R and Thacker J (1988) Six complementation groups for ionizing radiation sensitivity in Chinese hamster cells. Mutat Res 193: 139–144.Google Scholar
  52. Kasid U, Pfeifer A, Weichselbaum RR, Dritschilo A and Mark GE (1987) The raf oncolgene is associated with a radiation-resistant human laryngeal cancer. Science 237: 1039–1041.Google Scholar
  53. Kasid U, Pfeifer A, Brennan T, Beckett M, Weischelbaum RR, Dritschilo A and Mark GE (1989) Effect of anti-sense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous cell carcinoma. Science 243: 1354–1356.Google Scholar
  54. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B and Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51: 6304–6311.Google Scholar
  55. Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B and Fornace Jr. AJ (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71: 587–597.Google Scholar
  56. Kelland LR, Edwards SM and Steel GG (1987) Induction and rejoining of DNA double-strand breaks in human cervix carcinoma cell lines of differing radiosensitivity. Radiat Res 116: 526–538.Google Scholar
  57. Kemp LH, Sedgwick SG and Jeggo PA (1984) X-ray sensitive mutants of Chinese Hamster ovary cells defective in double strand break rejoining. Mutat Res 132: 189–196.Google Scholar
  58. Komatsu K, Okumura Y, Kodama S, Yoshida M and Miller RC (1989) Lack of correlation between radiosensitivity and inhibition of DNA synthesis in hybrids (A-T × HeLa). Int J Radiat Biol 56 (6): 863–867.Google Scholar
  59. Kuo SS, Saad AH, Koong AC, Hahn GM and Giaccia AJ (1993) Potassium-channel activation in response to low doses of gamma-irradiation involves reactive oxygen intermediates in nonexcitatory cells. Proc Natl Acad Sci USA 90: 908–912.Google Scholar
  60. Lehmann AR and Stevens S (1977) The production and repair of double-strand breaks in cells from normal humans and from patients with ataxiatelangectasia. Biochem Biophys Acta 474: 49–60.Google Scholar
  61. Lindahl T (1990) Repair of intrinsic DNA lesions. Mutat Res 238: 305–311.Google Scholar
  62. Lowe SW, Schmitt EM, Smith SW, Osborne BA and Jacks T (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362: 847–849.Google Scholar
  63. Madhukar BV, Oh SY, Chang CC, Wade M and Trosko JE (1989) Altered regulation of intercellular communication by epidermal growth factor, transforming growth factor-beta and peptide hormones in normal human keratinocytes. Carcinogenesis 10: 13–20.Google Scholar
  64. Mayne LV, Mullenders LHF and Van Zeeland AA (1988b) Cockayne's syndrome: a uv sensitive disorder with a defect in the repair of transcribing DNA but normal overall excision repair. In: Friedberg EC and Hanawalt PC (eds) Mechanisms and Consequences of DNA Damage Processing, Liss, New York, pp. 263–266.Google Scholar
  65. McClean S, Hosking LK and Hill BT (1993) Dominant expression of multiple drug resistance afterin vitro X-irradiation exposure in intraspecific Chinese hamster ovary hybrid cells. J Natl Cancer Inst 85: 48–53.Google Scholar
  66. McKenna WG, Nakahara K and Muschel RJ (1988) Site-specific integration of H-ras in transformed rat embryo cells. Science 241: 1325–1327.Google Scholar
  67. McKenna WG, Weiss MC, Endlich B, Ling CC, Bakanauskas VJ, Kelsten ML and Muschel J (1990a) Synergistic effect of the v-myc oncogene with H-ras on radioresistance. Cancer Res 50: 97–102.Google Scholar
  68. McKenna WG, Weiss MC, Bakanauskas V, Sandler H, Kelsten ML, Biaglow J, Tuttle S, Endlich B, Ling CC and Muschel J (1990b) The role of the H-ras oncogene in radiation resistance and metastasis. Int J Rad Oncol Biol Phys 18: 849–860.Google Scholar
  69. McKenna WG, Iliakis G, Weiss MC, Bernhard EJ and Muschell RJ (1991) Increased G2 delay in radiation-resistant cells obtained by transformation of primary rat embryo cells with the oncogenes H-ras and v-myc. Radiat Res 125: 283–287.Google Scholar
  70. McKinnon PJ (1987) Ataxia telangectasia: an inherited disorder of ionizingradiation sensitivity in man. Human Genet 75: 197–208.Google Scholar
  71. Mellon I, Spivak G and Hanawalt PC (1987) Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene. Cell 51: 241–249.Google Scholar
  72. Mignatti P, Morimoto T and Rifkin DB (1992) Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J Cell Physiol 151: 81–93.Google Scholar
  73. Musk SRR (1991) Reduction of radiation-induced cell cycle block by caffeine does not necessarily lead to increased cell killing. Radiat Res 125: 262–266.Google Scholar
  74. Nairn RS, Humphrey RM and Adair GM (1988) Transformation depending on intermolecular homologous recombination is stimulated by UV damage in transfected DNA. Mutat Res 208 (3–4): 137–141.Google Scholar
  75. Nishizuka Y (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258: 607–614.Google Scholar
  76. North P, Ganesh A and Thacker J (1990) The rejoining of double-strand breaks in DNA by human cell extracts. Nucleic Acids Res 18 (21): 6205–6210.Google Scholar
  77. Pardo FS, Ong A, Bristow RG, Taghian A and Borek C (1991) Role of transfection and clonal selection in mediating radioresistance. Proc Natl Acad Sci USA.Google Scholar
  78. Perera JR, Glasunov AV, Glaser VM and Boreiko AV (1988) Repair of double-strand breaks in plasmid DNA in the yeastSaccharomyces cerevisiae. Mol Gen Genet 213 (2–3): 421–424.Google Scholar
  79. Pirollo KF, Garner R, Yuan SY et al. (1989) Raf involvement in the simutaneous genetic transfer of the radioresistant and transforming phenotypes. Int J Radiat Biol 55: 783–796.Google Scholar
  80. Pirotton S, Boutherin Falson O, Robaye B and Boeynaems JM (1992) Ecto-phosphorylation on aortic endothelial cells. Exquisite sensitivity to staurosporine. Biochem J 285: 585–591.Google Scholar
  81. Pirotton S, Robaye B, Lagneau C and Boeynaems JM (1990) Adenine nucleotides modulate phosphatidylcholine metabolism in aortic endothelial cells. J Cell Physiol 142: 449–457.Google Scholar
  82. Powell SN and McMillan TJ (1991) Clonal variation in DNA repair in a human glioma cell line. Radiother Oncol 21: 225–232.Google Scholar
  83. Powell SN, Whitaker SJ, Edwards SM and McMillan TJ (1992) A DNA repair defect in a radiation-sensitive clone of a human bladder carcinoma cell line. Br J Cancer 65: 798–802.Google Scholar
  84. Powell SN, Whitaker S, Peacock JH and McMillan TJ (1993) Ataxia-telangietasia: an investigation of the repair defect in the cell line AT5BIVA by plasmid reconstitution. Mutat Res 294: 9–20.Google Scholar
  85. Powell SN and McMillan TJ (1993) Human tumor cell repair fidelity correlates with radioresistance. Int J Radiat Oncol Biol Phys.Google Scholar
  86. Protic-Sabljic M and Kraemer KH (1986) Host cell reactivation by human cells of DNA expression vectors damaged by ultraviolet radiation or by acid-heat treatment. Carcinogenesis 7 (10): 1765–1770.Google Scholar
  87. Rainbow AJ and Howes M (1981) Decreased repair of gamma-irradiated adenovirus in xeroderma pigmentosum fibroblasts. Int J Radiat Biol 36: 621–629.Google Scholar
  88. Rapaport E (1983) Treatment of human tumor cells with ADP or ATP yields arrest of growth in the S phase of the cell cycle. J Cell Physiol 114: 279–283.Google Scholar
  89. Roth DB, Menetski JP, Nakajima PB, Bosma MJ and Gellert M (199.) V(D)J Recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell 70 (6): 983–991.Google Scholar
  90. Schiestl RH, Reynolds P and Prakash S (1989) Cloning and sequence analysis ofSacharomyces cerevisiae RAD9 gene and further evidence that its product is required for cell cycle arrest induced by DNA damage. Mol Cell Biol 9: 1882–1896.Google Scholar
  91. Schwartz JL, Rotmensch J, Giovanazzi S, Cohen MB and Weichselbaum RR (1987) Faster repair of DNA double-strand breaks in radioresistant human tumor cells. Int J Radiat Oncol Biol Phys 15: 907–912.Google Scholar
  92. Sherman ML, Datta R, Hallahan DEet al. (in press) Protein kinase-C mediates inducibility of nuclear signal transducers EGR-1 and c-jun. Proc Natl Acad Sci USA.Google Scholar
  93. Singh SP and Lavin MF (1990) DNA-binding protein activated by gamma radiation in human cells. Mol Cell Biol 10: 5279–5285.Google Scholar
  94. Sklar MD (1988) Theras oncogenes increase the intrinsic resistance of NIH 3T3 cells to ionizing radiation. Science 239: 645–647.Google Scholar
  95. Skubitz KM and Goueli SA (1991) Basic fibroblast growth factor is a substrate for phosphorylation by human neutrophil ecto-protein kinase activity. Biochem Biophys Res Commun 174: 49–55.Google Scholar
  96. Subramani S (1989) Analysis of recombination in mammalian cells using SV40 and SV40 derived vectors. Mutat Res 220: 221–234.Google Scholar
  97. Terasima R and Tolmach LJ (1963) x-ray sensitivity and DNA synthesis in synchronous populations of HeLa cells. Science 140: 490–492.Google Scholar
  98. Terleth C, Waters R, Brouwer J and van de Putte P (1990) Differential repair of UV damage inSaccharomyces cerevisiae is cell cycle dependent. EMBO J 9: 2899–2904.Google Scholar
  99. Thacker J and Wilkinson RE (1991) The genetic basis of resistance to ionising radiation damage in cultured mammalian cells. Mutat Res 254: 135–142.Google Scholar
  100. Thaler DS, Stahl MM and Stahl FW (1987) Tests of the double-strand-break repair model for red-mediated recombination of phage lambda and plasmid lambda dv. Genetics 116 (4): 501–511.Google Scholar
  101. Thomas BJ and Rothstein R (1989) Elevated recombination rates in transcriptionally active DNA. Cell 56: 619–630.Google Scholar
  102. Thompson LH, Brookman KW, Jones NJ, Allen SA and Carrano AV (1990) Molecular cloning of the human XRCC-1 gene, which corrects defective DNA strand break repair and sister chromatid exchange. Mol. Cell Biol. 10 (12): 6160–6171.Google Scholar
  103. Trosko JE, Chang CC, Madhukar BV and Klaunig JE (1990) Chemical, oncogene and growth factor inhibition gap junctional intercellular communication: an integrative hypothesis of carcinogenesis. Pathobiology 58: 265–278.Google Scholar
  104. Tucker JD, Jones NJ, Allen NA, Minkler JL, Stewart SA, Thompson LH and Carrano AV (1991) Cytogenetic characterization of the ionizing radiation sensitive Chinese hamster mutant irs1. Mutat Res 254 (2): 143–152.Google Scholar
  105. Uckun FM, Tuel Ahlgren L, Song CW, Waddick K, Myers DE, Kirihara J, Ledbetter JA and Schieven GL (1992) Ionizing radiation stimulates unidentified tyrosine-specific protein kinases in human B-lymphocyte precursors, triggering apoptosis and clonogenic cell death. Proc Natl Acad Sci USA 89: 9005–9009.Google Scholar
  106. Uckun FM, Schieven GL, Tuel-Ahlgren LM, Dibirdik I, Myers DE, Ledbetter JA and Song CW (1993) Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C Signaling pathway in human B-lymphocyte precursors. Proc Natl Acad Sci USA 90 (1): 252–256.Google Scholar
  107. Usuki K, Heldin NE, Miyazono K, Ishikawa F, Takaku F, Westermark B and Heldin CH (1989) Production of plateletderived endothelial cell growth factor by normal and transformed human cells in culture. Proc Natl Acad Sci USA 86: 7427–7431.Google Scholar
  108. Usuki K, Miyazono K and Heldin CH (1991) Covalent linkage between nucleotides and platelet-derived endothelial cell growth factor. J Biol Chem 266: 20525–20531.Google Scholar
  109. Usuki K, Saras J, Waltenberger J, Miyazono K, Pierce G, Thomason A and Heldin CH (1992) Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. Biochem Biophys Res Commun 184: 1311–1316.Google Scholar
  110. Vilgrain I and Baird A (1991) Basic fibroblast growth factor is phosphorylated by an ecto-protein kinase associated with the surface of SK-Hep cells. Ann NY Acad Sci 638: 445–448.Google Scholar
  111. Vlodavsky I, Bar Shavit R, Ishai Michaeli R, Bashkin P and Fuks Z (1991) Extracellular sequestration and release of fibroblast growth factor: a regulatory mechanism? Trends Biochem Sci 16: 268–271.Google Scholar
  112. Vlodavsky I, Bashkin P, Ishai Michaeli R, Chajek Shaul T, Bar Shavit R, Haimovitz Friedman A, Klagsbrun M and Fuks Z (1991) Sequestration and release of basic fibroblast growth factor. Ann NY Acad Sci 638: 207–220.Google Scholar
  113. Wahls WP and Moore PD (1990) Relative frequencies of homologous recombination between plasmids introduced into DNA repair-deficient and other mammalian somatic cell lines. Somat Cell Mol Genet 16 (4): 321–329.Google Scholar
  114. Weichselbaum RR, Hallahan DE, Sukhatme V, Dritschilo A, Sherman ML and Kufe DW (1991) Biological consequences of gene regulation after ionizing radiation exposure. J Natl Cancer Inst 83: 480–484.Google Scholar
  115. Wlodek D and Hittelman WN (1987) The repair of doublestrand DNA breaks correlates with radiosensitivity of L5178Y-S and L5178Y-R cells. Radiat Res 112: 146–155.Google Scholar
  116. Zdzienicka MZ, Tran Q, van der Schans CP and Simons JWIM (1988) Characterization of an x-ray sensitive mutant of V79 Chinese hamster cells. Mutat Res 194: 239–243.Google Scholar
  117. Zheng LM, Zychlinsky A, Liu CC, Ojcius DM and Young JD (1991) Extracellular ATP as a trigger for apoptosis or programmed cell death. J Cell Biol 112: 279–288.Google Scholar

Copyright information

© Kluwer Academic Publishers 1993

Authors and Affiliations

  • Simon N. Powell
    • 1
  • Edward H. Abraham
    • 1
  1. 1.Department of Radiation OncologyMassachusetts General HospitalBostonUSA

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