Radiation-induced apoptosis

Cell and Tissue Research

Volumn 301, Issue 1, 2000, Pages 133-142

  Verheij, Marcel ^a   Bartelink, Harry ^a  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

Author keywords

Apoptosis; Caspases; Clonogenic survival; Ionizing radiation; P53; SAPK JNK; Signal transduction

Indexed keywords

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; BIOCHEMISTRY; CELL DEATH; HUMAN; HUMAN CELL; MOLECULAR BIOLOGY; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIATION; RADIATION RESPONSE; RADIOBIOLOGY; RADIOSENSITIVITY; RADIOTHERAPY; RAT; REGULATORY MECHANISM; REVIEW;

ANIMALIA;

EID: 0033929767     PISSN: 0302766X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s004410000188     Document Type: Review

References (133)

1. Adams JM, Cory S (1998) The Bcl-2 protein family:arbiters of cell survival. Science 281:1309-1312
2. Alnemri ES (1997) Mammalian cell death proteases:a family of highly conserved aspartate specific cysteine proteases. J Cell Biochem 64:33-42
3. Balaban N, Moni J, Shannon M, Dang L, Murphy E, Goldkorn T (1996) The effect of ionizing radiation on signal transduction: antibodies to EGF receptor sensitize A431 cells to radiation. Biochim Biophys Acta 1314:147-156
4. Barendsen GW (1982) Dose fractionation, dose rate, and isoeffect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys 8:1981-1997
5. Bedford JS (1991) Sublethal damage, potentially lethal damage, and chromosomal aberrations in mammalian cells exposed to ionizing radiations. Int J Radiat Oncol Biol Phys 21:1457-1469
6. Boesen-de Cock JGR, Tepper AD, Vries E de, Blitterswijk WJ van, Borst J (1998) CD95 (Fas/APO-1) induces ceramide formation and apoptosis in the absence of a functional acid sphingomyelinase. J Biol Chem 273:7560-7565
7. Bose R, Verheij M, Haimovitz-Friedman A, Scotto K, Fuks Z, Kolesnick R (1995) Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals. Cell 82:405-414
8. Bossy-Wetzel E, Bakiri L, Yaniv M (1997) Induction of apoptosis by the transcription factor c-Jun. EMBO J 16:1695-1709
9. Bracey TS, Miller JC, Preece A, Paraskeva C (1995) γ-Radiation-induced apoptosis in human colorectal adenoma and carcinoma cell lines can occur in the absence of wild type p53. Oncogene 10:2391-2396
10. Bristow RG, Benchimol S, Hill RP (1996) The p53 gene as a modifier of intrinsic radiosensitivity: implications for radiotherapy. Radiother Oncol 40:197-223
11. Cahill MA, Peter ME, Kischkel FC, Chinnaiyan AM, Dixit VM, Krammer PH, Nordheim A (1996) CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases. Oncogene 13:2087-2096
12. Canman CE, Kastan MB (1996) Signal transduction. Three paths to stress. Nature 384:213-214
13. Cardone M, Salvesen GS, Widmann C, Johnson G, Frisch SM (1997) The regulation of anoikis: MEKK-1 activation requires cleavage by caspases. Cell 90:315-323
14. Carter S, Auer KL, Reardon DB, Birrer M, Fisher PB, Valerie K, Schmidt-Ullrich R, Mikkelsen R, Dent P (1998) Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell killing by low dose ionizing radiation in A431 human squamous carcinoma cells. Oncogene 16:2787-2796
15. Chang HY, Nishitoh H, Yang X, Ichijo H, Baltimore D (1998) Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science 281:1860-1863
16. Chapman JD, Anderson PR (1999) Predicting and overcoming the radioresistance of individual tumors. Int J Radiat Oncol Biol Phys 44:477-479
17. Chauhan D, Kharbanda S, Ogata A, Urashima M, Teoh G, Robertson M, Kufe DW, Anderson KC (1997) Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. Blood 89:227-234
18. Chauhan D, Hideshima T, Treon S, Teoh G, Raje N, Yoshihimito S, Tai Y-T, Li W, Fan J, DeCaprio J, Anderson KC (1999) Functional interaction between retinoblastoma protein and stress-activated protein kinase in multiple myeloma cells. Cancer Res 59:1192-1195
19. Chen CH, Zhang J, Ling CC (1994) Transfected c-myc and c-Haras modulate radiation-induced apoptosis in rat embryo cells. Radiat Res 139:307-315
20. Chen M, Quintans J, Fuks Z, Thompson C, Kufe DW, Weichselbaum RR (1995) Suppression of bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor α, and ceramide. Cancer Res 55:991-994
21. Chen Y-R, Wang X, Templeton D, Davis RJ, Tan T-H (1996a) The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and γ radiation. J Biol Chem 271:31929-31936
22. Chen Y-R, Meyer CF, Tan T-H (1996b) Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in γ radiation-induced apoptosis. J Biol Chem 271:631-634
23. Chung EJ, Seong J, Yang WI, Park TK, Kim JW, Suh CO, Kim GE (1999) Spontaneous apoptosis as a predictor of radiotherapy in patients with stage IIB squamous cell carcinoma of the uterine cervix. Acta Oncol 38:449-454
24. Chyle V, Pollack A, Czerniak B, Stephens LC, Zagars GK, Terry NH, Meyn RE (1996) Apoptosis and downstaging after preoperative radiotherapy for muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys 2:281-287
25. Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, Wyllie AH (1993) Thymocyte apoptosis induced by p53-dependent and independent pathway. Nature 362:849-851
26. Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326:1-16
27. Cosulich S, Clarke P (1996) Apoptosis: does stress kill? Curr Biol 6:1586-1588
28. Datta R, Kojima H, Banach D, Bump NJ, Talanian RV, Alnemri ES, Weichselbaum RR, Wong WW, Kufe DW (1997) Activation of a CrmA-insensitive, p35-sensitive pathway in ionizing radiation-induced apoptosis. J Biol Chem 272:1965-1969
29. Dewey WC, Ling CC, Meyn RE (1995) Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys 33:781-796
30. Douglas BG, Fowler JF (1976) The effect of multiple small doses of X-rays on skin reactions in the mouse and basic interpretation. Radiat Res 66:401-426
31. Dubray B, Breton C, Delic J, Klijanienko J, Maciorowski Z, Vielh P, Fourquet A, Dumont J, Magdelenat H, Cosset J-M (1998) In vitro radiation-induced apoptosis and early response to low-dose radiotherapy in non-Hodgkin's lymphomas. Radiother Oncol 46:185-191
32. Ferrer I, Olivé M, Ribera J, Planas AM (1996) Naturally occurring (programmed) and radiation-induced apoptosis are associated with selective c-Jun expression in the developing rat brain. Eur J Neurosci 8:1286-1298
33. Friesen C, Herr I, Krammer PH, Debatin KM (1996) Involvement of the CD95 (APO-1/Fas) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat Med 2:574-577
34. Frisch SM, Vuori K, Kelaita D, Sicks S (1996) A role for Jun-N-terminal kinase in anoikis; suppression by bcl-2 and crmA. J Cell Biol 135:1377-1382
35. Fuchs SY, Adler V, Buschmann T, Yin Z, Wu X, Jones SN, Ronai Z (1998) JNK targets p53 ubiquitination and degradation in nonstressed cells. Genes Dev 12:2658-2663
36. Fuks Z, Vlodavsky I, Andreeff M, McLoughlin M, Haimovitz-Friedman A (1992) Effects of extracellular matrix on the response of endothelial cells to radiation in vitro. Eur J Cancer 28A:725-731
37. Fuks Z, Persaud RS, Alfieri A, McLoughlin M, Schwartz JL, Seddon A, Cordon-Cardo C, Haimovitz-Friedman A (1994) Basic fibroblast growth factor protects endothelial cells from radiation-induced programmed cell death in vitro and in vivo. Cancer Res 54:2582-2590
38. Giusti AM, Raimond M, Ravagnan G, Sapora O, Parasassi T (1998) Human cell membrane oxidative damage induced by single and fractionated doses of ionizing radiation: a fluorescence spectroscopy study. Int J Radiat Biol 74:595-605
39. Goillot E, Raingeaud J, Ranger A, Tepper RI, Davis RJ, Harlow E (1996) Mitogen-activated protein kinase-mediated Fas apoptotic signaling pathway. Proc Natl Acad Sci USA 94:3302-3307
40. Green D, Reed J (1998) Mitochondria and apoptosis. Science 281:1309-1312
41. Haimovitz-Friedman A, Vlodavsky I, Chaudhuri A, Witte L, Fuks Z (1991) Autocrine effects of fibroblast growth factor in repair of radiation damage in endothelial cells. Cancer Res 51: 2552-2558
42. Haimovitz-Friedman A, Balaban NA, McLoughlin M, Ehleiter D, Michaeli J, Vlodavsky I, Fuks Z (1994a) Protein kinase C mediates basic fibroblast growth factor protection of endothelial cells against radiation-induced apoptosis. Cancer Res 54:2591-2597
43. Haimovitz-Friedman A., Kan CC, Ehleiter D, Persaud RS, McLoughlin M, Fuks Z, Kolesnick RN (1994b) Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 180:525-535
44. Hallahan DE, Virydachalam S, Kuchibhotla J, Kufe DW, Weichselbaum RR (1994) Membrane-derived second messenger regulates X-ray-mediated tumor necrosis factor alpha gene induction. Proc Natl Acad Sci USA 91:4897-4901
45. Ham J, Babij C, Whitfield J, Pfarr CM, Lallemand D, Yaniv M, Rubin LL (1995) A c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron 14:927-939
46. Hannun YA (1996) Functions of ceramide in coordinating cellular responses to stress. Science 274:1855-1859
47. Havrilesky LJ, Elbendary A, Hurteau JA, Whitaker RS, Rodriguez GC, Berchuck A (1995) Chemotherapy-induced apoptosis in epithelial ovarian cancers. Obstet Gynecol 85:1007-1010
48. Hendry JH, Potten CS (1982) Intestinal cell radiosensitivity: a comparison for cell death assayed by apoptosis or by a loss of clonogenicity. Int J Radiat Biol 42:621-628
49. Herr I, Wilhelm D, Böhler T, Angel P, Debatin KM (1997) Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis. EMBO J 16:6200-6208
50. Hockenbery DM, Oltvai ZN, Yin X-M, Milliman CL, Korsmeyer SJ (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241-251
51. Hofmann K, Dixit VM (1998) Ceramide in apoptosis - does it really matter? Trends Biochem Sci 23:374-377
52. Huschtscha LI, Bartier WA, Ross CEA, Tattersall MHN (1996) Characteristics of cancer cell death after exposure to cytotoxic drugs in vitro. Br J Cancer 73:54-60
53. Ip YT, Davis RJ (1998) Signal transduction by the c-Jun N-terminal kinase (JNK) - from inflammation to development. Curr Opin Cell Biol 10:205-219
54. Kastan M (1997) On the TRAIL from p53 to apoptosis? Nat Genet 17:1317-1322
55. Kastan MB, Onyekwere O, Sidransky, D, Vogelstein B, Craig R (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51:6304-6311
56. Kastan MB, Zhan Q, El-Deiry W, Carrier F, Jachks T, Walsh W, Plunkett BS, Vogelstein B, Fornace AJ Jr (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71:587-597
57. Kataoka T, Schröter M, Hahne M, Schneider P, Irmler M, Thome M, Froelich CJ, Tschopp J (1998) FLIP prevents apoptosis induced by death receptors but not by perforin/granzyme B, chemotherapeutic drugs, and gamma irradiation. J Immunol 161:3936-3942
58. Kaufmann SH (1989) Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note. Cancer Res 49:5870-5878
59. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239-257
60. Kerr JFR, Winterford CM, Harmon BV (1994) Apoptosis: its significance in cancer and cancer therapy. Cancer 73:2013-2026
61. Kolesnick R (1991) Sphingomyelin and derivatives as cellular signals. Prog Lipid Res 30:1-38
62. Kolesnick R, Hannun YA (1999) Ceramide and apoptosis. Trends Biochem Sci 24:224-225
63. Kuo SS, Saad AS, Koong AC, Hahn GM, Giaccia AJ (1993) Potassium-channel activation in response to low doses of γ-irradiation involves reactive oxygen intermediates in nonexcitatory cells. Proc Natl Acad Sci USA 90:908-912
64. Langendijk JA, Thunnissen FBJM, Arends JW, Jong JMA de, Velde GPM ten, Lamers RJS, Wouters EFM (1998) Apoptosis in stage III non-small cell lung carcinoma (NSCLC) treated with high dose radiotherapy. Radiother Oncol 48 (Suppl 1): S195
65. Langlois NEI, Lamb J, Eremin O, Heys SD (1997) Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis, mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products. J Pathol 182:392-397
66. Lara PC, Perez S, Rey A, Santana C (1999) Apoptosis in carcinoma of the bladder: relation with radiation treatment results. Int J Radiat Oncol Biol Phys 43:1015-1019
67. Lavin M, Shiloh Y (1997) The genetic defect in ataxia-telangiectasia. Annu Rev Immunol 15:177-202
68. Lera J, Lara PC, Perez S, Cabrera JL, Santana C (1998) Tumor proliferation, p53 expression, and poptosis in laryngeal carcinoma. Relation to the results of radiotherapy. Cancer 83:2493-2501
69. Levine EL, Renehan A, Gossiel R, Davidson SE, Roberts SA, Chadwick C, Wilks DP, Potten CS, Hendry JH, Hunter RD, West CML (1995) Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma. Radiother Oncol 37:1-9
70. Ling CC, Chen CH, Li WX (1994a) Apoptosis induced at different dose rates: implications for the shoulder region of the cell survival curves. Radiother Oncol 33:11-16
71. Ling CC, Chen CH, Fuks Z (1994b) An equation for the dose response of radiation-induced apoptosis: possible incorporation with the LQ model. Radiother Oncol 33:17-22
72. Ling CC, Guo M, Chen CH, Deloherey T (1995a) Radiation-induced apoptosis - effect of cell age and dose fractionation. Cancer Res 55:5207-5212
73. Ling CC, Chen CH, Fuks Z (1995b) An equation for the dose response of radiation-induced apoptosis. Radiother Oncol 35:165-166
74. Logsdon MD, McDonald TJ, Pugh WC, Besa PC, Cox JD, Cabanillas F, Stephens LC, Meyn RE (1996) Apoptosis, Bcl-2, and BAX as predictors of tumor response in stage I and II follicular lymphoma. Int J Radiat Oncol Biol Phys 39:175
75. Lowe SW, Schmitt EM, Smith SW, Osborne BA, Jacks T (1993) P53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362:847-849
76. Malisan F, Testi R (1999) Lipid signaling in CD95-mediated apoptosis. FEBS Lett 452:100-103
77. Maundrell K, Antonsson B, Magnenat E, Camps M, Muda M, Chabert C, Gillieron C, Boschert U, Vial-Knecht E, Martinou JC, Arkinstall S (1997) Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinase in the presence of the constitutively active GTP-binding protein rac1. J Biol Chem 272:25238-25242
78. Merritt A, Potten C, Kemp C, Hickman J, Balmain A, Lane D, Hall P (1994) The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res 54:614-617
79. Meyn RE, Stephens LC, Ang KK, Hunter NR, Brock WA, Milas L, Peters LJ (1993) Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies. Int J Radiat Biol 64:583-591
80. Meyn RE, Stephens LC, Hunter NR, Ang KK, Milas L (1994a) Reemergence of apoptotic cells between fractionated doses in irradiated murine tumors. Int J Radiat Oncol Biol Phys 30: 619-624
81. Meyn RE, Stephens LC, Hendry JH (1994b) Workshop report: radiation-induced apoptosis, 5-8 May 1994, Round Top, Texas, USA. Int J Radiat Biol 66:655-659
82. Miller TM, Moulder KL, Knudson CM, Creedon DJ, Deshmukh M, Korsmeyer SJ, Johnson EM (1997) Bax deletion further orders the cell death pathway in cerebellar granule cells and suggests a caspase-independent pathway to cell death. J Cell Biol 139:205-217
83. Miura M, Zhu H, Rotello R, Hartweig EA, Yuan J (1993) Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75:653-660
84. Miyashita T, Kralewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC (1994) Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799-1805
85. Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293-299
86. Morgan SE, Kastan MB (1997) P53 and ATM: cell cycle, cell death, and cancer. Adv Cancer Res 71:1-25
87. Müller M, Strand S, Hug H, Heinemann EM, Walczak H, Hofmann WJ, Stremmel W, Krammer PH, Galle PR (1997) Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. J Clin Invest 99:403-413
88. Olson DR (1995) Calculation of the biological effect of fractionated radiotherapy: the importance of radiation-induced apoptosis. Br J Radiol 68:1230-1236
89. Pena LA, Fuks Z, Kolesnick R (1997) Stress-induced apoptosis and the sphingomyelin pathway. Biochem Pharmacol 53:615-621
90. Radford IR (1986) Evidence for a general relationship between the induced level of DNA double-strand breakage and cell killing after X-irradiation of mammalian cells. Int J Radiat Biol Rel Studies Phys Chem Med 49:611-620
91. Radford IR, Murphy TK (1994) 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 65:229-239
92. Ruiter GA, Zerp SF, Bartelink H, Blitterswijk WJ van, Verheij M (1999) Alkyl-lysophospholipids activate the SAPK/JNK pathway and enhance radiation-induced apoptosis. Cancer Res 59:2457-2463
93. Rupnow BA, Murtha AD, Alarcon RM, Giaccia AJ, Knox SJ (1998) Direct evidence that apoptosis enhances tumor responses to fractionated radiotherapy. Cancer Res 58:1779-1784
94. Sabapathy K, Hu Y, Kallunki T, Schreiber M, David J-P, Jochem W, Wagner EF, Karin M (1999) JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. Curr Biol 9:116-125
95. Salvesen GS, Dixit VM (1997) Caspases: intracellular signaling by proteolysis. Cell 91:443-446
96. Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin K-M, Krammer PH, Peter ME (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17:1675-1687
97. Schreiber M, Kolbus A, Piu F, Szabowski A, Mohle-Steinlein U, Tian J, Karin M, Angel P, Wagner EF (1999) Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev 13:607-619
98. Sentman CL, Shutter CL, Hockenberry D, Kanagaa O, Korsmeyer SJ (1991) Bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 67:879-888
99. Seymour CB, Mothersill C, Alper T (1986) High yields of lethal mutations in somatic mammalian cells that survive ionizing radiation. Int J Radiat Biol 50:167-169
100. Shaw P, Bovey R, Tardy S, Sahli R, Sordat B, Costa J (1992) Induction of apoptosis by wild-type p53 in a human colon tumour-derived cell line. Proc Natl Acad Sci USA 89:4495-4499
101. Sheridan MT, Cooper RA, West CML (1999) A high ratio of apoptosis to proliferation correlates with improved survival after radiotherapy for cervical adenocarcinoma. Int J Radiat Oncol Biol Phys 44:507-512
102. 2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor β-Lapachone-induced apoptosis through an oxidation-dependent pathway. Cancer Res 59:391-398
103. Shieh S-Y, Ikeda M, Taya Y, Prives C (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM 2. Cell 91:325-334
104. Shinomiya N, Shinomiya M, Wakiyama H, Katsura Y, Rokutanda M (1994) Enhancement of CDDP cytotoxicity by caffeine is characterized by apoptotic cell death. Exp Cell Res 210:236-242
105. Steel GG, McMillan TJ, Peacock JH (1989) The radiobiology of human cells and tissues. In vitro radiosensitivity. The picture has changed in the 1980s. Int J Radiat Biol 56:525-537
106. Steller H (1995) Mechanisms and genes of cellular suicide. Science 267:1445-1449
107. Stephens LC, Ang KK, Schultheiss TE, Milas L, Meyn RE (1991) Apoptosis in irradiated murine tumors. Radiat Res 127:308-316
108. Strasser A, Harris AW, Jacks T, Cory S (1994) DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2. Cell 79:189-192
109. Tepper AD, Vries E de, Blitterswijk WJ van, Borst J (1999) Ordering of ceramide formation, caspase activation, and mitochondrial changes during CD95-and DNA damage-induced apoptosis. J Clin Invest 103:971-978
110. Thames HD, Withers HR, Peters LJ, Fletcher GH (1982) Changes in early and late radiation responses with altered dose fractionation: implications for dose survival relationships. Int J Radiat Oncol Biol Phys 8:219-226
111. Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456-1462
112. 2+] in human epithelial tumor cells. Cancer Res 54:5224-5230
113. Trott KR (1972) Relation between division delay and damage expressed in later generations. Curr Top Radiat Res 7:336-337
114. Vaux DL (1993) Toward an understanding of the molecular mechanisms of physiological cell death. Proc Natl Acad Sci USA 90:786-789
115. Vaux DL, Haecker G, Strasser A (1995) An evolutionary perspective on apoptosis. Cell 76:777-779
116. Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, Birrer MJ, Szabo E, Zon LI, Kyriakis JM, Haimovitz-Friedman A, Fuks Z, Kolesnick RN (1996) Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380:75-79
117. Verheij M, Ruiter GA, Zerp SF, Blitterswijk WJ van, Fuks Z, Haimovitz-Friedman A, Bartelink H (1998) The role of the stress-activated protein kinase (SAPK/JNK) signaling pathway in radiation-induced apoptosis. Radiother Oncol 47:225-232
118. Vesalainen S, Lipponen P, Talja M, Syrjänen K (1994) Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 12:1797-1803
119. Villunger A, Egle A, Kos M, Hartmann BL, Geley S, Kofler R, Greil R (1997) Drug-induced apoptosis is associated with enhanced Fas (Apo-1/CD95) ligand expression but occurs independently of Fas (Apo-1/CD95) signaling in human T-acute lymphatic leukemia cells. Cancer Res 57:3331-3334
120. Walker PR, Smith C, Youdale T, Leblanc J, Whitfield JF, Sikorska M (1991) Topoisomerase II-reactive chemotherapeutic drugs induce apoptosis in thymocytes. Cancer Res 51:1078-1085
121. Wang T-H, Wang H-S, Ichijo H, Giannakakou P, Foster JS, Fojo T, Wimalasena J (1998) Microtubule-interfering agents activate c-Jun N-terminal kinase/stress-activated protein kinase through both Ras and apoptosis signal-regulating kinase pathways. J Biol Chem 273:4928-4936
122. Westwick JK, Bielawska AE, Dbaibo G, Hannun YA, Brenner DA (1995) Ceramide activates the stress-activated protein kinases. J Biol Chem 270:22689-22692
123. Wheeler JA, Stephens LC, Tornos C, Eifel PJ, Ang KK, Milas L, Allen PK, Meyn RE (1995) ASTRO research fellowship: apoptosis as a predictor of tumor response to radiation in stage IB cervical carcinoma. Int J Radiat Oncol Biol Phys 32: 1487-1493
124. Williams GT (1991) Programmed cell death: apoptosis and oncogenesis. Cell 65:1097-1098
125. Wilson DJ, Fortner KA, Lynch DH, Mattingly RR, Macara IG, Posada JA, Budd RC (1996) JNK, but not MAPK, activation is associated with Fas-mediated apoptosis in human T cells. Eur J Immunol 26:989-994
126. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326-1331
127. Xu Y, Baltimore D (1996) Dual roles of ATM in the cellular response to radiation and in cell growth control. Genes Dev 10:2401-2410
128. Yang D, Kuan C-Y, Whitmarsh AJ, Rincon M, Zheng TS, Davis RJ, Rakic P, Flavell RA (1997a) Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the JNK3 gene. Nature 389:865-870
129. Yang X, Khosravi-Far R, Chang HY, Baltimore D (1997b) Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell 89:1067-1076
130. Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M (1991) Wild-type p53 induces apoptosis in myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352:345-347
131. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme. Cell 75:641-652
132. Zanke BW, Boudreau K, Rubie E, Winnett E, Tibbies LA, Zon L, Kyriakis J, Liu F-F, Woodgett JR (1996) The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat. Curr Biol 6:606-613
133. Zhan Q, Fan S, Bae I, Guillouf C, Liebermann DA, O'Connor PM, Fornace AJ Jr (1994) Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene 9:3743-3751