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Radiation-induced apoptosis and its relationship to loss of clonogenic survival

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Abstract

Ionizing radiation can be an effective inducer of apoptosis and studies of many aspects of the pathways and mechanisms involved in this apoptosis induction have been published. This review stresses two aspects: the relationship between apoptosis and loss of clonogenic ability in irradiated cells and the time course for the appearance of apoptosis after radiation exposure. Although it was initially assumed that apoptosis occurred relatively quickly (within hours) after irradiation, evidence is presented and discussed here showing that apoptosis can occur at long times after irradiation (out to 20 days) in some cell types. This late, or delayed, apoptosis occurs after the cells have divided once or several times. The impact of delayed apoptosis on loss of clonogenicity after irradiation remains unclear. It seems likely that in some cell types, e.g., fibroblasts, the occurrence of late apoptosis is minimal and may have little impact on long term cell survival of the population, but in at least one instance, with a cell line of hematopoietic origin, it appears that late apoptosis can account for all the loss of clonogenicity in irradiated cells. The role of p53 in radiation-induced apoptosis is also discussed, with data presented showing that both p53-dependent and independent pathways for radiation-induced apoptosis exist, depending on the cell type.

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References

  1. Williams GT, Smith CA. Molecular regulation of apoptosis: Genetic controls on cell death. Cell 1993; 74: 777-779.

    Google Scholar 

  2. Kerr JFR, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer 1994; 73: 2013-2026.

    Google Scholar 

  3. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456-1462.

    Google Scholar 

  4. Hendry JH, Potten CS. Intestinal cell radiosensitivity: a comparison for cell death assayed by apoptosis or by a loss of clonogenicity. Int J Radiat Biol 1982; 42: 621-628.

    Google Scholar 

  5. Stephens LC, Schultheiss TE, Small SM, Ang KK, Peters LJ. Response of parotid gland organ culture to radiation. Radiat Res 1989; 120: 140-153.

    Google Scholar 

  6. Sellins KS, Cohen JJ. Gene induction by γ-irradiation leads to DNA fragmentation in lymphocytes. J Immunol 1987; 139: 3199-3206.

    Google Scholar 

  7. Stephens LC, Ang KK, Schultheiss TE, Milas L, Meyn RE. Apoptosis in irradiated murine tumors. Radiat Res 1991; 127: 308-316.

    Google Scholar 

  8. Stephens LC, Hunter NR, Ang KK, Milas L, Meyn RE. Development of apoptosis in irradiated murine tumors as a function of time and dose. Radiat Res 1993; 135: 75-80.

    Google Scholar 

  9. Meyn RE, Stephens LC, Ang KK, et al. Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies. Int J Radiat Biol 1993; 64: 583-591.

    Google Scholar 

  10. Langley RE, Palayoor ST, Coleman CN, Bump EA. Modifiers of radiation-induced apoptosis. Radiat Res 1993; 136: 320-326.

    Google Scholar 

  11. Radford IR, Murphy TK, Radley JM, Ellis SL. Radiation response of mouse lymphoid and myeloid cell lines. Part II. Apoptotic death is shown by all lines examined. Int J Radiat Biol 1994; 65: 217-227.

    Google Scholar 

  12. Story MD, Stephens LC, Tomasovic SP, Meyn RE. A role for calcium in regulating apoptosis in rat thymocytes irradiated in vitro. Int J Radiat Biol 1992; 61: 243-251.

    Google Scholar 

  13. Klassen NV, Walker PR, Ross CK, Cygler J, Lach B. Two-stage cell shrinkage and the OER for radiation-induced apoptosis of rat thymocytes. Int J Radiat Biol 1993; 64: 571-581.

    Google Scholar 

  14. Warters RL. Radiation-induced apoptosis in a murine T-cell hybridoma. Cancer Res 1992; 52: 883-890.

    Google Scholar 

  15. Langley RE, Palayoor ST, Coleman CN, Bump EA. Radiation-induced apoptosis in F9 teratocarcinoma cells. Int J Radiat Biol 1994; 65: 605-610.

    Google Scholar 

  16. Chen CH, Zhang J, Ling CC. Transfected c-myc and c-Ha-ras modulate radiation-induced apoptosis in rat embryo cells. Radiat Res 1994; 139: 307-315.

    Google Scholar 

  17. Tubiana M, Dutreix J, Wambersie A, Bewley DR Introduction to Radiobiology. New York, NY (USA): Taylor & Francis, 1990.

    Google Scholar 

  18. Hall EJ. Radiobiology for the Radiologist, 4th Edition. Philadelphia, PA (USA): J.B. Lippincott Company, 1994.

    Google Scholar 

  19. Haimovitz-Friedman A, Kolesnick RN, Fuks Z. Modulation of the apoptotic response: Potential for improving the outcome in clinical radiotherapy. Seminars in Radiation Oncology 1996; 6: 273-283.

    Google Scholar 

  20. Hallahan DE. Radiation-mediated gene expression in the pathogenesis of the clinical radiation response. Seminars in Radiation Oncology 1996; 6: 250-267.

    Google Scholar 

  21. Story MD, Voehringer DW, Malone CG, Hobbs ML, Meyn RE. Radiation-induced apoptosis in sensitive and resistant cells isolated from a mouse lymphoma. Int J Radiat Biol 1994; 66: 659-668.

    Google Scholar 

  22. Radford IR, Murphy TK. Radiation response of mouse lymphoid and myeloid cell lines. Part III. Different signals can lead to apoptosis and may influence sensitivity to killing by DNA double-strand breakage. Int J Radiat Biol 1994; 65: 229-239.

    Google Scholar 

  23. Olive PL, Frazer G, Banath JP. Radiation-induced apoptosis measured in the TK6 human B lymphoblast cells using the comet assay. Radiat Res 1993; 136: 130-136.

    Google Scholar 

  24. Vrdoljak E, Bill CA, Stephens LC, van der Kogel AJ, Ang KK, Tofilon PJ. Radiation-induced apoptosis of oligodendrocytes in vitro. Int J Radiat Biol 1992; 62: 475-480.

    Google Scholar 

  25. Hu Q, Hill RP. Radiosensitivity, apoptosis and repair of DNA double-strand breaks in radiation-sensitive Chinese hamster ovary cell mutants treated at different dose rates. Radiat Res 1996; 146: 636-645.

    Google Scholar 

  26. Bracey TS, Miller JC, Preece A, Paraskeva C. γ-Radiation-induced apoptosis in human colorectal adenoma and carcinoma cell lines can occur in the absence of wild type p53. Oncogene 1995; 10: 2391-2396.

    Google Scholar 

  27. Hendry JH, Potten CS, Chadwick C, Bianchi M. Cell death (apoptosis) in the mouse small intestine after low doses: effects of dose-rate, 14.7 MeV neutrons and 600 MeV (maximum energy) neutrons. Int J Radiat Biol 1982; 42: 611-620.

    Google Scholar 

  28. Wolf D, Rotter V. Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells. Proc Natl Sci 1985; 82: 790-794.

    Google Scholar 

  29. Potten CS. What is an apoptotic index measuring? A commentary. Br J Cancer 1996; 74: 1743-1748.

    Google Scholar 

  30. Mori N, Okumoto M, Morimoto J, et al. Genetic analysis of susceptibility to radiation-induced apoptosis of thymocytes in mice. Int J Radiat Biol 1992; 62: 153-159.

    Google Scholar 

  31. Ling Y-H, Priebe W, Perez-Soler R. Apoptosis induced by anthracycline antibiotics in P388 parent and multidrug-resistant cells. Cancer Res 1993; 53: 1845-1852.

    Google Scholar 

  32. Martin SJ, Lennon SV, Bonham AM, Cotter TG. Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis. J Immunol 1990; 145: 1859-1867.

    Google Scholar 

  33. Radford IR. Radiation response of mouse lymphoid and myeloid cell lines. Part I. Sensitivity to killing by ionizing radiation, rate of loss of viability, and cell type of origin. Int J Radiat Biol 1994; 65: 203-215.

    Google Scholar 

  34. Xia F, Wang X, Wang Y-H, et al. Altered p53 status correlates with differences in sensitivity to radiation-induced mutation and apoptosis in two closely related human lymphoblast lines. Cancer Res 1995; 55: 12-15.

    Google Scholar 

  35. Potten CS. Extreme sensitivity of some intestinal crypt cells to X and γ irradiation. Nature 1977; 269: 518-521.

    Google Scholar 

  36. Allan DJ, Gobe GC, Harmon BV. Sertoli cell death by apoptosis in the immature rat testis following X-irradiation. Scanning Microscopy 1988; 2: 503-512.

    Google Scholar 

  37. Li YQ, Guo YP, Jay V, Stewart PA, Wong CS. Time course of radiation-induced apoptosis in the adult rat spinal cord. Radiother Oncol 1996; 39: 35-42.

    Google Scholar 

  38. Aldridge DR, Arends MJ, Radford IR. Increasing the susceptibility of the rat 208F fibroblast cell line to radiation-induced apoptosis does not alter its clonogenic survival dose-response. Br J Cancer 1995; 71: 571-577.

    Google Scholar 

  39. McKenna WG, Bernhard EJ, Markiewicz DA, Rudoltz MS, Maity A, Muschel RJ. Regulation of radiation-induced apoptosis in oncogene-transfected fibroblasts: influence of H-ras on the G2 delay. Oncogene 1996; 12: 237-245.

    Google Scholar 

  40. Haas-Kogan D, Yount G, Haas M, et al. p53-dependent G1 arrest and p53-independent apoptosis influence the radiobiological response of glioblastoma. Int J Radiat Oncol Biol Phys 1996; 36: 95-103.

    Google Scholar 

  41. Hopcia KL, McCarey YL, Sylvester FC, Held KD. Radiation-induced apoptosis in HL60 cells: Oxygen effect, relationship between apoptosis and loss of clonogenicity, and dependence of time to apoptosis on radiation dose. Radiat Res 1996; 145: 315-323.

    Google Scholar 

  42. Tauchi H, Sawada S. Analysis of mitotic cell death caused by radiation in mouse leukemia L5178Y cells: apoptosis is the ultimate form of cell death following mitotic failure. Int J Radiat Biol 1994; 65: 449-455.

    Google Scholar 

  43. Yanagihara K, Nii M, Numoto M, et al. Radiation-induced apoptotic cell death in human gastric epithelial tumour cells; correlation between mitotic death and apoptosis. Int J Radiat Biol 1995; 67: 677-685.

    Google Scholar 

  44. Thompson LH, Suit HD. Proliferation kinetics of X-irradiated mouse L cells studied with time lapse photography. II. Int J Radiat Biol 1969; 15: 347-362.

    Google Scholar 

  45. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257.

    Google Scholar 

  46. Vidair CA, Chen CH, Ling CC, Dewey WC. Apoptosis induced by X-irradiation of rec-myc cells is postmitotic and not predicted by the time after irradiation or behavior of sister cells. Cancer Res 1996; 56: 4116-4118.

    Google Scholar 

  47. Kadhim MA, Lorimore SA, Townsend KMS, Goodhead DT, Buckle VJ, Wright EG. Radiation-induced genomic instability: delayed cytogenetic aberrations and apoptosis in primary human bone marrow cells. Int J Radiat Biol 1995; 67: 287-293.

    Google Scholar 

  48. Zhen W, Vaughan ATM. Effect of caffeine on radiation-induced apoptosis in TK6 cells. Radiat Res 1995; 141: 170-175.

    Google Scholar 

  49. Hagan MP, Hopcia KL, Sylvester FC, Held KD. Caffeine induced apoptosis reveals a persistent lesion after BrdUrd/UVB-light treatment. Radiat Res 1997; 147: 674-679.

    Google Scholar 

  50. Jamali M, Trott K-R. Persistent increase in the rates of apoptosis and dicentric chromosomes in surviving V79 cells after X-irradiation. Int J Radiat Biol 1996; 70: 705-709.

    Google Scholar 

  51. Allan DJ. Radiation-induced apoptosis: its role in a MADCaT (mitosis-apoptosis-differentiation calcium toxicity) scheme of cytotoxicity mechanisms. Int J Radiat Biol 1992; 62: 145-152.

    Google Scholar 

  52. Dive C, Hickman JA. Drug-target interactions: only the first step in the commitment to a programmed cell death? Br J Cancer 1991; 64: 192-196.

    Google Scholar 

  53. Eastman A. Activation of programmed cell death by anticancer agents: Cisplatin as a model system. Cancer Cells 1990; 2: 275-280.

    Google Scholar 

  54. Colombel M, Olsson CA, Ng P-Y, Buttyan R. Hormone-regulated apoptosis results from reentry of differentiated prostate cells into a defective cell cycle. Cancer Res 1992; 52: 4313-4319.

    Google Scholar 

  55. Kruman II, Matylevich NP, Beletsky IP, Afanasyev VN, Umansky SR. Apoptosis of murine BW5147 thymoma cells induced by dexamethasone and γ-irradiation. J Cell Physiol 1991; 148: 267-273.

    Google Scholar 

  56. Palayoor ST, Macklis RM, Bump EA, Coleman CN. Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells. Radiat Res 1995; 141: 235-243.

    Google Scholar 

  57. Gorczyca W, Bigman K, Mittelman A, et al. Induction of DNA strand breaks associated with apoptosis during treatment of leukemias. Leukemia 1993; 7: 659-670.

    Google Scholar 

  58. Gorczyca W, Gong J, Ardelt B, Traganos F, Darzynkiewicz Z. The cell cycle related differences in susceptibility of HL-60 cells to apoptosis induced by various antitumor agents. Cancer Res 1993; 53: 3186-3192.

    Google Scholar 

  59. Han Z, Chatterjee D, He DM, et al. Evidence for a G2 checkpoint in p53-independent apoptosis induction by X-irradiation. Mol Cell Biol 1995; 15: 5849-5857.

    Google Scholar 

  60. Tolmach LJ, Busse PW. The action of caffeine on X-irradiated HeLa cells. IV. Progression delays and enhanced cell killing at high caffeine concentrations. Radiat Res 1980; 82: 374-392.

    Google Scholar 

  61. Efferth T, Fabry U, Glatte P, Osieka R. Expression of apoptosis-related oncoproteins and modulation of apoptosis by caffiene in human leukemic cells. J Cancer Res Clin Oncol 1995; 121: 648-656.

    Google Scholar 

  62. Ling CC, Guo M, Chen CH, Deloherey T. Radiation-induced apoptosis: Effects of cell age and dose fractionation. Cancer Res 1995; 55: 5207-5212.

    Google Scholar 

  63. Olive PL, Banath JP, Durand RE. Development of apoptosis and polyploidy in human lymphoblast cells as a function of position in the cell cycle at the time of irradiation. Radiat Res 1996; 146: 595-602.

    Google Scholar 

  64. Russell J, Wheldon TE, Stanton P. A radioresistant variant derived from a human neuroblastoma cell line is less prone to radiation-induced apoptosis. Cancer Res 1995; 55: 4915-4912.

    Google Scholar 

  65. Fan S, El-Deiry WS, Bae I, et al. p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res 1994; 54: 5824-5830.

    Google Scholar 

  66. Okada, S. Radiation Biochemistry. Vol. I. Cells. New York: Academic Press, 1970.

    Google Scholar 

  67. Mirkovic N, Meyn RE, Hunter NR, Milas L. Radiation-induced apoptosis in a murine lymphoma in vivo. Radiother Oncol 1994; 33: 11-16.

    Google Scholar 

  68. Warenius HM, Down JD. RBE of fast neutrons for apoptosis in mouse thymocytes. Int J Radiat Biol 1995; 68: 625-629.

    Google Scholar 

  69. Bernhard EJ, Muschel RJ, Bakanauskas VJ, McKenna WG. Reducing the radiation-induced G2 delay causes HeLa cells to undergo apoptosis instead of mitotic death. Int J Radiat Biol 1996; 69: 575-584.

    Google Scholar 

  70. Orrenius S, McConkey DJ, Nicotera P. Role of calcium in toxic and programmed cell death. Adv Exp Med Biol 1991; 283: 419-425.

    Google Scholar 

  71. Richter C. Pro-oxidants and mitochondrial Ca2+: their relationship to apoptosis and oncogenesis. FEBS Lett 1993; 325: 104-107.

    Google Scholar 

  72. Voehringer DW, Story MD, O'Neil RG, Meyn RE. Modulating Ca2+ in radiation-induced apoptosis suppresses DNA fragmentation but does not enhance clonogenic survival. Int J Radiat Biol 1997; 71: 237-243.

    Google Scholar 

  73. Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Seminars in Cancer Biology 1994; 4: 327-332.

    Google Scholar 

  74. Sakakura C, Sweeney EA, Shirahama T, et al. Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis. Int J Cancer 1996; 67: 101-105.

    Google Scholar 

  75. Puthenveettil JA, Frederickson SA, Reznikoff CA. Apoptosis in human papillomavirus 16 E7-, but not E6-immortalized human uroepithelial cells. Oncogene 1996; 13: 1123-1131.

    Google Scholar 

  76. Dewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys 1995; 33: 781-796.

    Google Scholar 

  77. Algan O, Stobbe CC, Helt AM, Hanks GE, Chapman JD. Radiation inactivation of human prostate cancer cells: The role of apoptosis. Radiat Res 1996; 146: 267-275.

    Google Scholar 

  78. Ling CC, Chen CH, Li WX. Apoptosis induced at different dose rates: implication for the shoulder region of cell survival curves. Radiother Oncol 1994; 32: 129-136.

    Google Scholar 

  79. Abend M, Rhein A, Gilbertz K-P, Blakely WF, van Beuningen D. Correlation of micronucleus and apoptosis assays with reproductive cell death. Int J Radiat Biol 1995; 67: 315-326.

    Google Scholar 

  80. Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell 1992; 70: 523-526.

    Google Scholar 

  81. Stewart BW. Mechanisms of apoptosis: Integration of genetic, biochemical, and cellular indicators. JNCI 1994; 86: 1286-1296.

    Google Scholar 

  82. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 in the cellular response to DNA damage. Cancer Res 1991; 51: 6304-6311.

    Google Scholar 

  83. Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB. Wild-type p53 is a cell cycle checkpoint determinant following radiation. Proc Natl Sci 1992; 89: 7491-7495.

    Google Scholar 

  84. Biard DSF, Martin M, Le Rhun Y, et al. Concomitant p53 gene mutation and increased radiosensitivity in rat lung embryo epithelial cells during neoplastic development. Cancer Res 1994; 54: 3361-3364.

    Google Scholar 

  85. Slichenmyer WJ, Nelson WG, Slebos RJ, Kastan MB. Loss of a p53-associated G1 checkpoint does not decrease cell survival following DNA damage. Cancer Res 1993; 53: 4164-4168.

    Google Scholar 

  86. Brachman DG, Beckett M, Graves D, Haraf D, Vokes E, Weichselbaum RR. p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res 1993; 53: 3667-3669.

    Google Scholar 

  87. Lee JM, Bernstein A. p53 mutations increase resistance to ionizing radiation. Proc Natl Sci 1993; 90: 5742-5746.

    Google Scholar 

  88. O'Connor PM, Jackman J, Jondle D, Bhatia K, Magrath I, Kohn KW. Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines. Cancer Res 1993; 53: 4776-4780.

    Google Scholar 

  89. McIlwrath AJ, Vasey PA, Ross GM, Brown R. Cell cycle arrests and radiosensitivity of human tumor cell lines: Dependence on wild-type p53 for radiosensitivity. Cancer Res 1994; 54: 3718-3722.

    Google Scholar 

  90. Bristow RG, Jang A, Peacock J, Chung S, Benchimol S, Hill RP. Mutant p53 increases radioresistance in rat embryo fibroblasts simultaneously transfected with HPV16-E7 and/or activated H-ras. Oncogene 1994; 9: 1527-1526.

    Google Scholar 

  91. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 1993; 362: 847-849.

    Google Scholar 

  92. Clarke AR, Purdie CA, Harrison DJ, et al. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 1993; 362: 849-852.

    Google Scholar 

  93. Lotem J, Sachs L. Hematopoietic cells from mice deficient in wild-type p53 are more resistant to induction of apoptosis by some agents. Blood 1993; 82: 1092-1096.

    Google Scholar 

  94. Radford IR. p53 status, DNA double-strand break repair proficiency, and radiation response of mouse lymphoid and myeloid cell lines. Int J Radiat Biol 1994; 66: 557-560.

    Google Scholar 

  95. Strasser A, Harris AW, Jacks T, Cory S. DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by bcl-2. Cell 1994; 79: 329-339.

    Google Scholar 

  96. Seki H, Kanegane H, Iwai K, et al. Ionizing radiation induces apoptotic cell death in human TcR-γ/δ+ T and natural killer cells without detectable p53 protein. Eur J Immunol 1994; 24: 2914-2917.

    Google Scholar 

  97. Merritt AJ, Potten CS, Kemp CJ, et al. The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res 1994; 54: 614-617.

    Google Scholar 

  98. Lowe SW, Bodis S, McClatchey A, et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994; 266: 807-810.

    Google Scholar 

  99. Haas-Kogan DA, Dazin P, Hu L, Deen DF, Israel MA. p53-independent apoptosis: A mechanism of radiation-induced cell death of glioblastoma cells. Cancer J Sci Am 1996; 2: 114-121.

    Google Scholar 

  100. Yount GL, Haas-Kogan DA, Vidair CA, Haas M, Dewey WC, Israel MA. Cell cycle synchrony unmasks the influence of p53 function on radiosensitivity of human glioblastoma cells. Cancer Res 1996; 56: 500-506.

    Google Scholar 

  101. Meyn RE, Stephens LC, Mason KA, Medina D. Radiation-induced apoptosis in normal and pre-neoplastic mammary glands in vivo: Significance of gland differentiation and p53 status. Int J Cancer 1996; 65: 466-472.

    Google Scholar 

  102. Wyllie AH. Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an overview. Cancer Metastasis Rev 1992; 11: 95-103.

    Google Scholar 

  103. Wheeler JA, Stephens LC, Tornos C, et al. ASTRO research fellowship: Apoptosis as a predictor of tumor response to radiation in stage IB cervical carcinoma. Int J Radiat Oncol Biol Phys 1995; 32: 1487-1493.

    Google Scholar 

  104. Chyle V, Pollack A, Czerniak B, et al. Apoptosis and downstaging after preoperative radiotherapy for muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys 1996; 35: 281-287.

    Google Scholar 

  105. Levine EL, Renehan A, Gossiel R, et al. Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma. Radiother Oncol 1995; 37: 1-9.

    Google Scholar 

  106. Pilepich MV, Krall J, Al-Sarraf M, et al. A phase III trial of androgen suppression before and during radiation therapy (RT) for locally advanced prostate carcinoma: a preliminary report of RTOG protocol 8610. Proc ASCO 1993; 12: 229.(Abstract)

    Google Scholar 

  107. Berges RR, Furuya Y, Remington L, English HF, Jacks T, Isaacs JT. Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation. Proc Natl Sci 1993; 90: 8910-8914.

    Google Scholar 

  108. Haimovitz-Friedman A, Kan C, Ehleiter D, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 1994; 180: 525-535.

    Google Scholar 

  109. Stapper NJ, Stuschke M, Sak A, Stuben G. Radiation-induced apoptosis in human sarcoma and glioma cell lines. Int J Cancer 1995; 62: 58-62.

    Google Scholar 

  110. Santana P, Pena LA, Haimovitz-Friedman A, et al. Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell 1996; 86: 189-199.

    Google Scholar 

  111. Fuks Z, Alfieri A, Haimovitz-Friedman A, Seddon A, Cordon-Cardo C. Intravenous basic fibroblast growth factor protects the lung but not the mediastinal organs against radiation-induced apoptosis in vivo. Cancer J 1995; 1: 62-72.

    Google Scholar 

  112. Manome Y, Weichselbaum RR, Kufe DW, Fine HA. Effect of bcl-2 on ionizing radiation and 1-β-D-arabinofuranosylcytosine-induced internucleosomal DNA fragmentation and cell survival in human myeloid leukemia cells. Oncology Res 1993; 5: 139-144.

    Google Scholar 

  113. Chen M, Quintans J, Fuks Z, Thompson C, Kufe DW, Weichselbaum RR. Suppression of bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor α, and ceramide. Cancer Res 1995; 55: 991-994.

    Google Scholar 

  114. Kitada S, Krajewski S, Miyashita T, Krajewska M, Reed JC. γ-Radiation induces upregulation of Bax protein and apoptosis in radiosensitive cells in vivo. Oncogene 1996; 12: 187-192.

    Google Scholar 

  115. Haas-Kogan DA, Kogan SC, Levi D, et al. Inhibition of apoptosis by the retinoblastoma gene product. EMBO J 1995; 14: 461-472.

    Google Scholar 

  116. Oren M. The involvement of oncogenes and tumor suppressor genes in the control of apoptosis. Cancer Metastasis Rev 1992; 11: 141-148.

    Google Scholar 

  117. Ling CC, Chen CH, Fuks Z. An equation for the dose response of radiation-induced apoptosis: possible incorporation with the LQ model. Radiother Oncol 1994; 33: 17-22.

    Google Scholar 

  118. Evans HH, Ricanati M, Horng MF, Jiang Q, Mencl J, Olive P. DNA double-strand break rejoining deficiency in TK6 and other human B-lymphoblast cell lines. Radiat Res 1993; 134: 307-315.

    Google Scholar 

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    K. D. Held

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Held, K.D. Radiation-induced apoptosis and its relationship to loss of clonogenic survival. Apoptosis 2, 265–282 (1997). https://doi.org/10.1023/A:1026485003280

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