Potential molecular targets for manipulating the radiation response

International Journal of Radiation Oncology Biology Physics

Volumn 37, Issue 3, 1997, Pages 639-653

  Maity, Amit ^a   Kao, Gary D ^a   Muschel, Ruth J ^a   Mckenna, W Gillies ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Apoptosis; Cell cycle checkpoints; Cyclins; DNA damage and repair; Gene induction; p53; Signal transduction

Indexed keywords

DNA; PROTEIN KINASE; RAS PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

APOPTOSIS; ARTICLE; CELL CYCLE; DNA DAMAGE; DNA REPAIR; FIBROSIS; GENE INDUCTION; IONIZING RADIATION; PNEUMONIA; PRIORITY JOURNAL; RADIATION RESPONSE; RADIOSENSITIVITY; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CELL CYCLE; DNA DAMAGE; DNA REPAIR; ENZYME ACTIVATION; GENE EXPRESSION; GENES, IMMEDIATE-EARLY; HUMANS; ONCOGENES; PROTEIN KINASE C; PROTO-ONCOGENES; SIGNAL TRANSDUCTION;

EID: 0030953485     PISSN: 03603016     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0360-3016(96)00598-6     Document Type: Article

References (180)

1. Aldridge, D. R.; Arends, M. J.; Radford, I. R. Increasing the susceptibility of the rat 208F fibroblast cell line to radiation-induced apoptosis does not alter its clonogenic survival. Br. J. Cancer 71:571-577; 1995.
2. Anderson, C. W. DNA damage and the DNA-activated protein kinase. Trends Biochem. Sci. 18:433-437; 1993.
3. Anscher, M. S.; Crocker, I. R.; Jirtle, R. L. Transforming growth factor-β1 expression in irradiated liver. Radiat. Res. 122:77-85; 1990.
4. Anscher, M. S.; Murase, T.; Prescott, D. M.; Marks, L. B.; Reisenbichler, H.; Bentel, G. C.; Spencer, D.; Sherouse, G.; Jirtle, R. L. Changes in plasma TGFβ levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis. Int. J. Radiat. Oncol. Biol. Phys. 30:671-676; 1994.
5. Anscher, M. S.; Peters, W. P.; Reisenbichler, H.; Petros, W. P.; Jirtle, R. J. Transforming growth factor β as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer. N. Engl. J. Med. 328:1592-1598; 1993.
6. Araki, S.; Shimada, Y.; Kaji, K.; Hayashi, H. Apoptosis of vascular endothelial cells by fibroblast growth factor deprivation. Biochem. Biophys. Res. Commun. 168:1194-1200; 1990.
7. Barcellos-Hoff, M. H. Radiation-induced transforming growth factor b and subsequent extracellular matric reorganization in murine mammary gland. Cancer Res. 53:3880-3886; 1993.
8. Bernhard, E.; Maity, A.; Muschel, R. J.; McKenna, W. G. Increased expression of cyclin B1 mRNA coincides with diminished G2-phase arrest in irradiated HeLa cells treated with staurosporine or caffeine. Radiat. Res. 140:393-400; 1994.
9. Bernhard, E. J.; Kao, G.; Cox, A. D.; Sebti, S. M.; Hamilton, A. D.; Muschel, R. J.; McKenna, W. G. The farnesyltransferase inhibitor FT1-277 radiosensitizes H-ras transformed rat embryo fibroblasts. Cancer Res. 56:1727-1730; 1996.
10. Bernhard, E. J.; Muschel, R. J.; Bakanauskas, V. J.; McKenna, W. G. Reducing the radiation-induced G2 delay causes HeLa cells to undergo apoptosis instead of mitotic death. Int. J. Radiat. Biol. 69:575-584; 1996.
11. Biederman, K. A.; Sun, J.; Giaccia, A. J.; Tosto, L. M.; Brown, J. M. scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. Proc. Natl. Acad. Sci. USA 88:3394-1397; 1991.
12. Bissonnette, R. P.; Echeverri, F.; Mahboubi, A.; Green, D. R. Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359:552-554; 1992.
13. Blobe, G. C.; Obeid, L. M.; Hannun, Y. A. Regulation of protein kinase C and role in cancer biology. Cancer Metastasis Rev. 13:411-431; 1994.
14. Boothman, D. A.; Bouvard, I.; Hughes, E. N. Identification and characterization of X-ray induced proteins in human cells. Cancer Res. 49:2871-2878; 1989.
15. Boothman, D. A.; Meyers, M.; Fukunaga, N.; Lee, S. W. Isolation of x-ray inducible transcripts from radioresistant human melanoma cells. Proc. Natl. Acad. Sci. USA 90:7200-7204; 1993.
16. Border, W. A.; Okuda, S.; Languino, L. R.; Sporn, M. B.; Ruoslahti, E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor b1. N. Engl. J. Med. 346:371-374; 1990.
17. Brach, M. A.; Ralf, H.; Sherman, M. L.; Gunji, H.; Weichselbaum, R. R.; Kufe, D. W. Ionizing radiation induces expression and binding activity of the nuclear factor NK-κB. J. Clin. Invest. 88:691-695; 1991.
18. Bristow, R. G.; Jang, A.; Peacock, J.; Chung, S.; Benchimol, S.; Hill, R. P. Mutant p53 increases radioresistance in rat embryo fibroblasts simultaneously transfected with HPV16-E7 and/or activated H-ras. Oncogene 9:1527-1536; 1994.
19. Busse, P. M.; Bose, S. K.; Jones, R. W.; Tolmach, L. J. The action of caffeine on X-irradiated HeLa Cells. III. Enhancement of X-ray induced killing during G2 arrest. Radiat. Res. 76:292-307; 1978.
20. Cano, E.; Mahadevan, L. C. Parallel signal processing among mammalian MAPKs. Trends Biochem. Sci. 20:117-122; 1995.
21. Castilla, A.; Prieto, J.; Fausto, N. Transforming growth factors b1 and a in chronic liver disease. Effects of interferon alpha therapy. N. Engl. J. Med. 324:933-940; 1991.
22. Chae, H. P.; Jarvis, L. J.; Uckun, F. M. Role of tyrosine phosphorylation in radiation-induced activation of c-jun protooncogene in human lymphohematopoetic precursor cells. Cancer Res. 53:447-451; 1993.
23. Chittenden, T.; Harrington, E. A.; O'Connor, R.; Flemington, C.; Lutz, R. J.; Evan, G. I.; Guild, B. C. Induction of apoptosis by the bcl-2 homologue Bak. Nature 374:733-736; 1995.
24. Clarke, A. R.; Purdie, C. A.; Harrison, D. J.; Morris, R. G.; Bird, C. C.; Hooper, M. L.; Wyllie, A. H. Thymocyte apoptosis is induced by p53-dependent and independent pathways. Nature 362:849-852; 1993.
25. Collins, M. K. L.; Marvel, J.; Malde, P.; Lopez-Rivas, A. Interleukin 3 protects murine bone marrow cells from apoptosis induced by DNA damaging agents. J. Exp. Med. 176:1043-1051; 1992.
26. Cullivier, O.; Pirianov, G.; Kleuser, B.; Vanek, P. G.; Coso, O. A.; Gutkind, J. S.; Spiegel, S. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature 381:800-803; 1996.
27. Datta, R.; Rubin, E.; Sukhatme, V.; Qureshi, S.; Hallahan, D.; Weichselbaum, R. R.; Kufe, D. W. Ionizing radiation activates transcription of the EGRI gene via CArG elements. Proc. Natl. Acad. Sci. USA 89:10149-10153; 1992.
28. Debenham, P. G.; Jones, N. J.; Webb, M. B. T. Vector-mediated DNA double-strand break repair analysis in normal, and radiation-sensitive, Chinese hamster V9 cells. Mutat. Res. 199:1-9; 1988.
29. Debenham, P. G.; Webb, M. B. T.; Jones, N. J.; Cox, R. Molecular studies on the nature of the repair defect in ataxia-telangiectasia and their implications for cellular radiobiology. J. Cell Sci. (Suppl. 6): 177-184; 1987.
30. Dulic, V.; Kaufmann, W. K.; Wilson, S. J.; Tlsty, T. D.; Lees, E.; Harper, J. W.; Elledge, S. J.; Reed, S. I. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76:1013-1023; 1994.
31. El-Deiry, W. S.; Harper, J. W.; O'Connor, P. M.; Veculescu, V. E.; Canman, C. E.; Jackman, J.; Pietenpol, J. A.; Burrell, M.; Hill, D. E.; Wang, Y.; Wiman, K. G.; Mercer, W. E.; Kohn, K. W.; Elledge, S. J.; Kinzler, K. W.; Vogelstein, B. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 54:1169-1174; 1994.
32. El-Deiry, W. S.; Tokino, T.; Velculescu, V. E.; Levy, D. B.; Parsons, R.; Trent, J. M.; Lin, D.; Mercer, W. E.; Kinzler, K. W.; Vogelstein, B. WAF1, a potent mediator of p53 tumor suppression. Cell 75:817-825; 1993.
33. Elkind, M. N. DNA damage and cell killing. Cause and effect? Cancer 56:2351-2362; 1985.
34. Evan, G. I.; Wyllie, A. H.; Gilbert, C. S.; Littlewood, T. D.; Land, H.; Brooks, M.; Waters, C. M.; Penn, L. Z.; Hancock, D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69:119-128; 1992.
35. Fan, S.; El-Deiry, W.; Bae, I.; Freeman, J.; Jondle, D.; Bhatia, K.; Fornace, A. J.; Magrath, I.; Kohn, K. W.; O'Connor, P. M. p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res. 54:5824-5830; 1994.
36. Fan, S.; Smith, M. L.; Rivet, D. J.; Duba, D.; Zhan, Q.; Kohn, K. W.; Fornace, A. J.; O'Connor, P. M. Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. Cancer Res. 55:1649-1654; 1995.
37. Fanidi, A.; Harrington, E. A.; Evan, G. I. Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature 359:554-556; 1992.
38. Fitzgerald, T. J.; Rothstein, L. A.; Daugherty, C.; McKenna, M.; Kase, K.; Greenberger, J. S. The activated human N-ras oncogene enhances x-irradiation repair of mammalian cells in vitro less effectively at low-dose rate: Implications for increased therapeutic ratio of low-dose irradiation. Am. J. Clin. Oncol. 8:517-522; 1985.
39. Fornace, A. J. Mammalian genes induced by radiation: Activation of genes associated with growth control. Annu. Rev. Genet. 26:507-526; 1992.
40. Fuks, Z.; Persaud, R. S.; Alfieri, A.; McLoughlin, M.; Ehleiter, D.; Schwartz, J. L.; Seddon, A. P.; Cordon-Cardo, C.; Haimovitz-Friedman, A. Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Res. 54:2582-2590; 1994.
41. Fulop, G. M.; Phillips, R. A. The scid mutation in mice causes a general defect in DNA repair. Nature 347:479-482; 1990.
42. Gewirtz, A. M. Oligodeoxynucleotide-based therapeutics for human leukemias. Stem Cells. 11 (Suppl. 3):96-103; 1993.
43. Giaccia, A.; Weinstein, R.; Hu, J.; Stamato, T. D. Cell cycle-dependent repair of double-strand breaks in a g-ray sensitive Chinese hamster cell. Somatic Cell Mol. Genet. 11:485-491; 1985.
44. Haimovitz-Friedman, A.; Balaban, N.; McLoughlin, M.; Ehleiter, D.; Michaeli, J.; Vlodavsky, I.; Fuks, Z. Protein kinase C mediates basic fibroblast growth factor protection of endothelial cells against radiation-induced apoptosis. Cancer Res. 54:2591-2597; 1994.
45. Haimovitz-Friedman, A.; Kan, C. C.; Ehleiter, D.; Persaud, R. S.; McLoughlin, M.; Fuks, Z.; Kolesnick, R. N. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J. Exp. Med. 180:525-535; 1994.
46. Haimovitz-Friedman, A.; Vlodavsky, I.; Chaudhuri, A.; Witte, L.; Fuks, Z. Autocrine effects of fibroblast growth factors in repair of radiation damage in endothelial cells. Cancer Res. 51:2552-2558; 1991.
47. Hallahan, D.; Clark, E. T.; Kuchibhotla, J.; Gewertz, B. L.; Collins, T. E-selectin gene induction by ionizing radiation is independent of cytokine induction. Biochem. Biophys. Res. Commun. 217:784-795; 1995.
48. Hallahan, D.; Virudachalam, S.; Schwartz, L.; Panje, N.; Mustafi, R.; Weichselbaum, R. R. Inhibition of protein kinases sensitizes human tumor cells to ionizing radiation. Radiat. Res. 129:345-350; 1992.
49. Hallahan, D.; Virudachalam, S.; Sherman, M.; Kufe, D.; Weichselbaum, R. Tumor necrosis factor gene expression is mediated by protein kinase C following activation by ionizing radiation. Cancer Res. 51:4565-4569; 1991.
50. Hallahan, D. E.; Beckett, M. A.; Kufe, D. W.; Weichselbaum, R. R. Interaction between recombinant tumor necrosis factor and radiation in 13 human tumor lines. Int. J. Radiat. Oncol. Biol. Phys. 19:69-74; 1990.
51. Hallahan, D. E.; Dunphy, E.; Virudachalam, S.; Sukhatme, V. P.; Kufe, D. W.; Weichselbaum, R. R. c-jun and Egr-1 participate in DNA synthesis and cell survival in response to ionizing radiation exposure. J. Biol. Chem. 270:30303-30309: 1995.
52. Hallahan, D. E.; Guis, D.; Kuchibhotla, J.; Sukhatme, V.; Kufe, D. W.; Weichselbaum, R. R. Radiation signaling mediated by jun activation following dissociation from a cell type-specific repressor. J. Biol. Chem. 268:4903-4907; 1993.
53. Hallahan, D. E.; Spriggs, D. R.; Beckett, M. A.; Kufe, D. W.; Weichselbaum, R. R. Increased tumor necrosis factor a mRNA after cellular exposure to ionizing radiation. Proc. Natl. Acad. Sci. USA 88:10104-10197; 1989.
54. Hallahan, D. E.; Sukhatme, V. P.; Sherman, M. L.; Virudachalam, S.; Kufe, D. W.; Weichselbaum, R. R. Protein kinase C mediates x-ray inducibility of nuclear signal transducers EGR1 and JUN. Proc. Natl. Acad. Sci. USA 88:2156-2160; 1991.
55. Hallahan, D. E.; Virudachalan, S.; Kuchibhotla, J.; Kufe, D. W.; Weichselbaum, R. R. Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor a gene induction. Proc. Natl. Acad. Sci. USA 91:4897-4901; 1994.
56. Harper, J. W.; Adami, G. R.; Wei, N.; Keyomarsi, K.; Elledge, S. J. The p21 cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75:805-816; 1993.
57. Harrington, E. A.; Bennett, M. R.; Fanidi, A.; Evan, G. I. c-Myc induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 13:3286-3295; 1994.
58. Hartwell, L. H.; Kastan, M. B. Cell cycle control and cancer. Science 266:1821-1828; 1994.
59. Hass-Kogan, D. A.; Kogan, S. C.; Levi, D.; Dazin, P.; T' Ang, A.; Fung, Y.-K. T.; Israel, M. A. Inhibition of apoptosis by the retinoblastoma gene product. EMBO J. 14:461-472; 1995.
60. Hendry, J. H.; Potten, C. S. Intestinal cell radiosensitivity: A comparison for cell death assayed by apoptosis or by a loss of clonogenicity. Int. J. Radiat. Biol. 42:621-628; 1982.
61. Hermeking, H.; Eick, D. Mediation of c-myc-induced apoptosis by p53. Nature 265:2091-2093; 1994.
62. Herrlich, P.; Ponta, H.; Rahmsdorf, H. J. DNA damage-induced gene expression: Signal transduction and relation to growth factor signaling. Rev. Physiol. Biochem. Pharmacol. 119:187-223; 1992.
63. Hickman, J. A. Apoptosis induced by anticancer drugs. Cancer Metastasis Rev. 11:121-139; 1992.
64. Hockenberry, D. M.; Oltvai, Z. N.; Yin, X. M.; Millimam, C. L.; Korsmeyer, S. J. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241-251; 1993.
65. Hollstein, M.; Sidransky, D.; Vogelstein, B.; Harris, C. C. p53 mutations in human cancers. Science 253:49-53; 1991.
66. Iliakis, G.; Metzger, L.; Muschel, R. J.; McKenna, W. G. Induction and repair of DNA double strand breaks in radiation-resistant cells obtained by transformation of primary rat embryo cells with the oncogenes H-ras and V-myc. Cancer Res. 50:6575-6579; 1990.
67. Jacobson, M. D.; Raff, M. C. Programmed cell death and Bcl-2 protection in very low oxygen. Nature 374:814-816; 1995.
68. Jung, M.; Zhang, Y.; Lee, S.; Dritschilo, A. Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha. Science 268:1619-1621; 1995.
69. Kane, D. J.; Safafian, T. A.; Anton, R.; Hahn, H.; Gralla, E. B.; Valentine, J. S.; Ord, T.; Bredesen, D. E. Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262:1274-1277; 1993.
70. Karin, M.; Smeal, T. Control of transcription factors by signal transduction pathways: the beginning of the end. Trends Biochem. Sci. 17:418-422; 1992.
71. Kasid, U.; Pfeifer, A.; Brennan, T.; Beckett, M.; Weichselbaum, R. R.; Dritschilo, A.; Mark, G. E. Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma. Science 243:1354-1356; 1989.
72. Kasid, U.; Pfeifer, A.; Weichselbaum, R. R.; Dritschilo, A.; Mark, G. E. The raf oncogene is associated with the radiation-resistant laryngeal cancer. Science 237:1039-1041; 1987.
73. Kasid, U.; Pirollo, K.; Dritschilo, A.; Chang, E. Oncogenic basis of radiation resistance. Adv. Cancer Res. 61:195-233; 1993.
74. Kastan, M. B.; Onyekwere, O.; Sidransky, D.; Vogelstein, B.; Craig, R. W. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51:6304-6311; 1991.
75. Kastan, M. B.; Zhan, Q.; El-Deiry, W. S.; Carrier, F.; Jacks, T.; Walsh, W. V.; Plunkett, B. S.; Vogelstein, B.; Fornace, A. J. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71:587-597; 1992.
76. Kelland, L. R.; Edwards, S. M.; Steel, G. G. Induction and rejoining of DNA double-strand breaks in human cervix carcinoma cell lines of differing radiosensitivity. Radiat. Res. 116:526-538; 1988.
77. Kemp, L. M.; Sedgwick, S. G.; Jeggo, P. A. X-ray sensitive mutants of Chinese hamster ovary cells defective in double-strand break rejoining. Mutat. Res. 132:189-196; 1984.
78. Kerr, L. D.; Inoue, J.; Verma, I. M. Signal transduction: the nuclear target. Curr. Opin. Cell Biol. 4:496-501; 1992.
79. Keyomarsi, K.; Sandoval, L.; Band, V.; Pardee, A. B. Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res. 51:3602-3609; 1991.
80. Kharbanda, K.; Yuan, Z.-M.; Rubin, E.; Weichselbaum, R.; Kufe, D. Activation of src-like p56/p53lyn tyrosine kinase by ionizing radiation. J. Biol. Chem. 269:20739-20743; 1994.
81. Kharbanda, S.; Ren, R.; Pandey, P.; Shafman, T. D.; Feller, S. M.; Weichselbaum, R. R.; Kufe, D. W. Activation of the c-Ab1 tyrosine kinase in the stress response to DNA-damaging agents. Nature 376:785-788; 1995.
82. Kharbanda, S.; Saleem, A.; Shafman, T.; Emoto, Y.; Taneja, N.; Rubin, E.; Weichselbaum, R.; Woodgett, J.; Avruch, J.; Kyriakis, J.; Kufe, D. Ionizing radiation stimulates a Grb2-mediated association of the stress-activated protein kinase with phosphtidylinositol 3-kinase. J. Biol. Chem. 270:18871-18874; 1995.
83. Kharbanda, S.; Saleem, A.; Shafman, T.; Emoto, Y.; Weichselbaum, R.; Kufe, D. Activation of the pp90rsk and mitogen-activated serine/threonine protein kinases by ionizing radiation. Proc. Natl. Acad. Sci. USA 91:5416-5420; 1994.
84. Kiehntopf, M.; Esquivel, E. L.; Brach, M. A.; Herrmann, F. Clinical applications of ribozymes. Lancet 345:1027-1031; 1995.
85. Kim, C. Y.; Giaccia, A. J.; Strulovici, B.; Brown, J. M. Differential expression of protein kinase C epsilon protein in lung cancer cell lines by ionising radiation. Br. J. Cancer 66:844-849; 1992.
86. Kim, S. H.; Khil, M. S.; Ryu, S.; Kim, J. H. Enhancement of radiation response on human carcinoma cells in culture by pentoxifylline. Int. J. Radiat. Oncol. Biol. Phys. 25:61-65; 1993.
87. Kinzler, K. W.; Vogelstein, B. Cancer therapy meets p53. N. Engl. J. Med. 331:49-50; 1994.
88. Kirchgessner, C. U.; Patil, C. K.; Evans, J. W.; Cuomo, C. A.; Fried, L. M.; Carter, T.; Oettinger, M. A.; Brown, J. M. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267:1178-1182; 1995.
89. Kolesnick, R.; Golde, D. W. The sphingomyelin pathway in tumor necrosis factor in interleukin-1 signaling. Cell 77:325-328; 1994.
90. Kuerbitz, S. J.; Plunkett, B. S.; Walsh, W. V.; Kastan, M. B. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc. Natl. Acad. Sci. USA 89:7491-7495; 1992.
91. Lee, J. M.; Bernstein, A. p53 mutations increase resistance to ionizing radiation. Proc. Natl. Acad. Sci. USA 90:5742-5746; 1993.
92. Lees-Miller, S. P.; Godbout, R.; Chan, D. W.; Weinfeld, M.; Day, R. S.; Barron, G. M.; Allalunis-Turner, J. Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell lines. Science 267:1183-1185; 1995.
93. Lehmann, A. R. Workshop on eukaryotic DNA repair genes and gene products. Cancer Res. 55:968-970; 1995.
94. Li, R.; Waga, S.; Hannon, G. J.; Beach, D.; Stillman, B. Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature 371:534-537; 1994.
95. Ling, C. C.; Endlich, B. Radioresistance induced by oncogenic transformation. Radiat. Res. 120:267-279; 1989.
96. cdc2 tyrosine dephosphorylation, and mitotic progression in Chinese hamster ovary cells exposed to etoposide. Cancer Res. 52:1817-1822; 1992.
97. Lowe, S. W.; Ruley, H. E.; Jacks, T.; Houseman, D. E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957-967; 1993.
98. Lowe, S. W.; Schmitt, E. M.; Smith, S. W.; Osborne, B. A.; Jacks, T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362:847-849; 1993.
99. Maity, A.; McKenna, W. G.; Muschel, R. J. Evidence for posttranscriptional regulation of cyclin B1 mRNA in the cell cycle and following irradiation in HeLa cells. EMBO J. 14:603-609; 1995.
100. Maity, A.; McKenna, W. G.; Muschel, R. J. The molecular basis for cell cycle delays following ionizing radiation: A review. Radiother. Oncol. 31:1-13; 1994.
101. McIlwrath, A. J.; Vasey, P. A.; Ross, G. M.; Brown, R. Cell cycle arrests and radiosensitivity of human tumor cell lines: Dependence on wild-type p53 for radiosensitivity. Cancer Res. 54:3718-3722; 1994.
102. McKenna, W. G.; Bernhard, E. J.; Markiewicz, D. A.; Rudoltz, M. S.; Maity, A.; Muschel, R. J. Regulation of radiation-induced apoptosis in oncogene-transfected fibroblasts: influence of H-ras on the G2 delay. Oncogene 12:237-245;1996.
103. McKenna, W. G.; Iliakis, G.; Weiss, M. C.; Bernhard, E. J.; Muschel, R. J. 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; 1991.
104. McKenna, W. G.; Weiss, M. C.; Endlich, B.; Ling, C. C.; Bakanauskas, V. J.; Kelsten, M. L.; Muschel, R. J. Synergistic effect of the v-myc oncogene with H-ras on radioresistance. Cancer Res. 50:97-102; 1990.
105. McKinnon, P. J. Ataxia-telangiectasia: An inherited disorder of ionizing-radiation sensitivity in man. Hum. Genet. 75:197-208; 1987.
106. Merritt, A. J.; Potten, C. S.; Kemp, C. J.; Hickman, J. A.; Balmain, A.; Lane, D. P.; Hall, P. A. 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; 1994.
107. Miller, A. C.; Kariko, K.; Myers, C. E.; Clark, E. P.; Samid, D. Increased radioresistance of EJras-transformed human osteosarcoma cells and its modulation by lovastatin, an inhibitor of p21ras isoprenylation. Int. J. Cancer 53:302-307; 1993.
108. Mimori, T.; Hardin, J. A.; Steitz, J. A. Characterization of the DNA-binding protein antigen Ku recognized by autoantibodies from patients with rheumatic disorders. J. Biol. Chem. 261:2274-2278; 1986.
109. Miyashita, T.; Krajewski, S.; Krajewski, M.; Wang, H. G.; Lin, H. K.; Liebermann, D. A.; Hoffman, B.; Reed, J. C. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9:1799-1805; 1994.
110. Morgan, D. O. Principles of CDK regulation. Nature 374:131-134; 1995.
111. Morgenbesser, S. D.; Williams, B. O.; Jacks, T.; DePinho, R. A. p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens. Nature 371:72-74; 1994.
112. Muschel, R. J.; Bernhard, E. J.; Garza, L.; McKenna, W. G.; Koch, C. J. Induction of apoptosis at different oxygen tensions: evidence that oxygen radicals do not mediate apoptotic signalling. Cancer Res. 55:995-998; 1995.
113. Muschel, R. J.; Zhang, H. B.; Iliakis, G.; McKenna, W. G. Cyclin B expression in HeLa cells during the G2 block induced by ionizing radiation. Cancer Res. 51:5113-5117; 1991.
114. Muschel, R. J.; Zhang, H. B.; McKenna, W. G. Differential effect of ionizing radiation on the expression of cyclin A and cyclin B in HeLa Cells. Cancer Res. 53:1128-1135; 1993.
115. Norbury, C.; Nurse, P. Animal cell cycles and their control. Annu. Rev. Biochem. 61:441-470; 1992.
116. O'Connor, P. M.; Ferris, D. K.; Pagano, M.; Draetta, G.; Pines, J.; Hunter, T.; Longo, D. L.; Kohn, K. W. G2 delay induced by nitrogen mustard in human cells affects cyclin A/Cdk2 and cyclin B1/Cdc2-kinase complexes differently. J. Biol. Chem. 268:8298-8308; 1993.
117. O'Connor, P. M.; Jackman, J.; Jondle, D.; Bhatia, K.; Magrath, I.; Kohn, K. W. Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines. Cancer Res. 53:4776-4780; 1993.
118. Obeid, L. M.; Linardic, C. M.; Karolak, L. A.; Hannun, Y. A. Programmed cell death induced by ceramide. Science 259:1769-1771; 1993.
119. Oltvai, Z. N.; Korsmeyer, S. J. Checkpoints of dueling dimers foil death wishes. Cell 79:189-192; 1994.
120. Oltvai, Z. N.; Milliman, C. L.; Korsmeyer, S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609-619; 1993.
121. Pan, H.; Griep, A. E. Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development. Genes Dev. 8:1285-1299; 1994.
122. Pardo, F. S.; Su, M.; Borek, C.; Preffer, F.; Dombkowski, D.; Gerweck, L.; Schmidt, E. V. Transfection of rat embryo cells with mutant p53 increases the intrinsic radiation resistance. Radiat. Res. 140:180-185; 1994.
123. Paules, R. S.; Levedakou, E. N.; Wilson, S. J.; Innes, C. L.; Rhodes, N.; Tlsty, T. D.; Galloway, D. A.; Donehower, L. A.; Tainsky, M. A.; Kaufmann, W. K. Defective G2 checkpoint function in cells from individuals with familial cancer syndromes. Cancer Res. 55:1763-1773; 1995.
124. Pergola, F.; Zdzienicka, M. Z.; Lieber, M. R. VD(J) recombination in mammalian cell mutants defective in DNA double-strand break repair. Mol. Cell Biol. 13:3464-3471; 1993.
125. Pirollo, K. F.; Garner, R.; Yuan, S. Y.; Li, L.; Blattner, W. A.; Chang, E. H. Raf involvement in the simultaneous genetic transfer of the radioresistant and transforming phenotypes. Int. J. Radiat. Biol. 55:783-796; 1989.
126. Powell, S. N.; DeFrank, J. S.; Connell, P.; Eogan, M.; Preffer, F.; Dombkowski, D.; Tang, W.; Friend, S. Differential sensitivity of p53(-) and p53(+) cells to caffeine-induced radiosensitization and override of G2 delay. Cancer Res. 55:1643-1648; 1995.
127. Prendergast, G. C.; Gibbs, J. B. Ras regulatory interactions: novel targets for anti-cancer intervention? Bioessays 16:187-191; 1994.
128. Radford, I. R. 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. 49:611; 1986.
129. Rotello, R. J.; Lieberman, R. C.; Purchio, A. F.; Gerschenson, L. E. Coordinated regulation of apoptosis and cell proliferation by transforming growth factor b1 in cultured uterine epithelial cells. Proc. Natl. Acad. Sci. USA 88:3412-3415; 1991.
130. Rubin, P.; Finkelstein, J.; Shapiro, D. Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: Interrelationship between alveolar macrophage and the septal fibroblast. Int. J. Radiat. Oncol. Biol. Phys. 24:183-184; 1992.
131. Russell, K. J.; Wiens, L. W.; Deniers, G. W.; Galloway, D. A.; Plon, S. E.; Groudine, M. Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells. Cancer Res. 55:1639-1642; 1995.
132. Samid, D.; Miller, A. C.; Rimoldi, D.; Gafner, J.; Clark, E. P. Increased radiation resistance in transformed and non-transformed cells with elevated ras proto-oncogene expression. Radiat. Res. 126:244-250; 1991.
133. Sancar, A. Mechanisms of DNA excision repair. Science 266:1954-1956; 1994.
134. Savitsky, K.; Bar-Shira, A.; Gilad, S.; Rotman, G.; Ziv, Y.; Vanagaite, L.; Tagle, D. A.; Smith, S.; Uziel, T.; Sfez, S.; Ashkenazi, M.; Pecker, I.; Frydman, M.; Harnik, R.; Patanjali, S. R.; Simmons, A.; Clines, G. A.; Sartiel, A.; Gatti, R. A.; Chessa, L.; Sanal, O.; Lavin, M. F.; Jaspers, N. G. J.; Malcolm, A.; Taylor, R.; Arlett, C. F.; Miki, T.; Weissman, S. M.; Lovett, M.; Collins, F. S.; Shiloh, Y. A single ataxia telangiectasia gene with a product similar to a PI-3 kinase. Science 268:1749-1753; 1995.
135. Scheffner, M.; Werness, B. A.; Huibregtse, J. M.; Levine, A. J.; Howley, P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129-1136; 1990.
136. Schwartz, J. L.; Rotmensch, J.; Giovanazzi, S.; Cohen, M. B.; Weichselbaum, R. R. Faster repair of DNA double-strand breaks in radioresistant human tumor cells. Int. J. Radiat. Oncol. Biol. Phys. 15:907-912; 1988.
137. Sellins, K. S.; Cohen, J. J. Hyperthermia induces apoptosis in thymocytes. Radiat. Res. 126:88-95; 1991.
138. Sentman, C. L.; Shutter, J. R.; Hockenberry, D.; Kanagawa, O.; Korsmeyer, S. J. Bcl-2 inhibits multiple form of apoptosis but not negative selection in thymocytes. Cell 67:879-888; 1991.
139. Shafman, T. D.; Saleem, A.; Kyriakis, J.; Weichselbaum, R.; Kharbanda, S.; Kufe, D. W. Defective induction of stress-activated protein kinase activity in ataxia-telangiectasia cells exposed to ionizing radiation. Cancer Res. 55:3242-3245; 1995.
140. Shaw, P.; Bovey, R.; Tardy, S.; Sahli, R.; Sordat, B.; Costa, J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc. Natl. Acad. Sci. USA 89:4495-4499; 1992.
141. Sherman, M. L.; Datta, R.; Hallahan, D. E.; Weichselbaum, R. R.; Kufe, D. W. Ionizing radiation regulates the expression of the c-jun protooncogene. Proc. Natl. Acad. Sci. USA 87:5663-5666; 1990.
142. 1 cyclins. Cell 73:1059-1065; 1993.
143. Sherr, C. J.; Roberts, J. M. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 9:1149-1163; 1995.
144. Shimizu, S.; Eguchi, Y.; Kosaka, H.; Kamiike, W.; Matsuda, H.; Tsujimoto, Y. Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL. Nature 374:811-813; 1995.
145. Sklar, M. D. The ras oncogenes increase the intrinsic resistance of NIH/3T3 cells to ionizing radiation. Science 239:645-647; 1988.
146. Slichenmyer, W. J.; Nelson, W. G.; Slebos, R. J.; Kastan, M. B. Loss of a p53 associated G1 checkpoint does not decrease cell curvival following DNA damage. Cancer Res. 53:4164-4168; 1993.
147. Smider, V.; Rathmell, W. K.; Lieber, M. R.; Chu, G. Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science 266:288-291; 1994.
148. Smith, M. L.; Chen, I. T.; Zhan, Q.; Bae, I.; Chen, C.; Gilmer, T. M.; Kastan, M. B.; O'Connor, P. M.; Fornace, A. J. Interaction of the p53-regulated protein gadd 45 with proliferating cell nuclear antigen. Science 266:1376-1379; 1994.
149. Smith, P. F.; Grossman, S. J.; Gerson, R. J.; Gordon, L. R.; Deluca, J. G.; Majka, J. A.; Wang, R. W.; Germer-shausen, J. I.; MacDonald, J. S. Studies on the mechanism of simvastatin-induced thyroid hypertrophy and follicular cell adenoma in the rat. Toxicol. Pathol. 19:197-205; 1991.
150. Stabnel, S. Protein kinase C-an enzyme and its relatives. Semin. Cancer Biol. 5:277-284; 1994.
151. Stein, C. A.; Cheng, Y. C. Antisense oligonucleotides as therapeutic agents - Is the bullet really magical? Science 261:1004-1012; 1993.
152. Stephens, L. C.; Ang, K. K.; Schultheiss, T. E.; Milas, L.; Meyn, R. E. Apoptosis in irradiated murine tumors. Radiat. Res. 127:308-316; 1991.
153. Stevenson, M. A.; Pollock, S. S.; Coleman, C. N.; Calderwood, S. K. X-irradiation, phorbol esters, and H2O2 stimulate mitogen-activated protein kinase activity in NIH-3T3 cells through the formation of reactive oxygen intermediates. Cancer Res. 54:12-15; 1994.
154. Story, M. D.; Voeringer, D. W.; Malone, C. G.; Hobbs, M. L.; Meyn, R. E. Radiation-induced apoptosis in sensitive and resistant cells isolated from a mouse lymphoma. Int. J. Radiat. Biol. 66:659-668; 1994.
155. Strasser, A.; Harris, A. W.; Jacks, T.; Cory, S. DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by bcl-2. Cell 79:329-339; 1994.
156. Su, L. N.; Little, J. B. Prolonged cell cycle delay in radioresistant human cell lines transfected With activated ras oncogene and/or simian virus 40 T-antigen. Radiat. Res. 133:73-79; 1993.
157. Taccioli, G. E.; Gottlieb, T. M.; Blunt, T.; Priestley, A.; Demengeot, J.; Mizuta, R.; Lehmann, A. R.; Alt, F. W.; Jackson, S. P.; Jeggo, P. A. Ku80: Product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 265:1442-1445; 1994.
158. Taccioli, G. E.; Rathbun, G.; Oltz, E.; Stamato, T.; Jeggo, P. A.; Alt, F. W. Impairment of V(D)J recombination in double-strand break repair mutants. Science 260:207-210; 1993.
159. Tepper, C. G.; Jayadev, S.; Liu, B.; Bielawska, A.; Wolff, R.; Yonehara, S.; Hannun, Y. A.; Seldin, M. F. Role for ceramide as an endogenous mediator of Fas-induced cytotoxicity. Proc. Natl. Acad. Sci. USA 92:8443-8447; 1995.
160. Thacker, J.; Ganesh, A. N. DNA-break repair, radioresistance of DNA synthesis, and camptothecin sensitivity in the radiation-sensitive irs mutants: comparisons to ataxia-telangiectasia cells. Mutat. Res. 235:49-58; 1990.
161. Thompson, L. H.; Brookman, K. W.; Dillehay, L. E.; Carrano, A. V.; Mazrimas, J. A.; Mooney, C. L.; Minkler, J. L. A CHO-cell strain having hypersensitivity to mutagens, a defect in DNA strand-break repair, and an extraordinary baseline frequency of sister-chromatid exchange. Mutat. Res. 95:427-440; 1982.
162. Thompson, L. H.; Brookman, K. W.; Jones, N. J.; Allen, S. A.; Carrano, A. V. Molecular cloning of the human XRCC1 gene, which corrects detective DNA strand break repair and sister chromatid exchange. Mol. Cell Biol. 10:6160-6171; 1990.
163. Tobey, R. A. Different drugs arrest cells at a number of distinct stages in G2. Nature 254:245-247; 1975.
164. Uckun, F. M.; Gillis, S.; Souza, L.; Song, C. W. Effects of recombinant growth factors on radiation survival of human bone marrow progenitor cells. Int. J. Radiat. Oncol. Biol. Phys. 16:415-435; 1989.
165. Uckun, F. M.; Schieven, G. L.; Park, C. H.; Dibirdik, I.; Smith, R. S.; Song, C. W.; Meyers, D. E.; Tuel-Ahlgren, L. M. Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of protein kinase C signalling pathway in human B-lymphocyte precursors. Proc. Natl. Acad. Sci. USA 90:252-256; 1993.
166. Uckun, F. M.; Tuel-Ahlgren, L.; Song, C. W.; Waddick, K.; Myers, D. E.; Kirihara, J.; Ledbetter, J. A.; Schieven, G. L. 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; 1992.
167. Verheij, M.; Bose, R.; Lin, X. H.; Yao, B.; Jarvis, W. D.; Grant, S.; Birrer, M. J.; Szabo, E.; Zon, L. I.; Kryakis, J. M.; Haimovitz-Friedman, A.; Fuks, Z.; Kolesnick, R. N. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380:75-79; 1996.
168. Ward, J. F. DNA damage produced by ionizing radiation in mammalian cells:identities, mechanisms of formation and reparability. Prog. Nucleic Acid. Mol. Biol. 56:95; 1988.
169. Weichselbaum, R. R.; Hallahan, D.; Fuks, Z.; Kufe, D. Radiation induction of immediate early genes: Effectors of the radiation-stress response. Int. J. Radiat. Oncol. Biol. Phys. 30:229-234; 1994.
170. Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell 81:323-330; 1995.
171. Weinert, T. A.; Hartwell, L. H. The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 241:317-322; 1988.
172. Witte, L.; Fuks, Z.; Haimovitz-Friedman, A.; Vlodavsky, I.; Goodman, D. S.; Eldor, A. Effects of irradiation on the release of growth factors from cultured bovine, porcine and human endothelial cells. Cancer Res 489:5066-5072; 1989.
173. Wlodek, D.; Hittelman, W. N. The repair of double-strand DNA breaks correlates with radiosensitivity of L5178Y-S and L5178Y-R cells. Radiat. Res. 112:146-155; 1987.
174. Woloshak, G. E.; Chang-Liu, G.-M.; Jones, P. S.; Jones, C. A. Modulation of gene expression in murine and hamster embryo cells following ionizing radiation. Cancer Res. 50:339-344; 1990.
175. Wyllie, A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555; 1980.
176. Wyllie, A. H.; Kerr, J. F. R.; Currie, A. R. Cell death: the significance of apoptosis. Int. Rev. Cytol. 68:251-305; 1980.
177. Xia, Z.; Dickens, M.; Raingeaud, J.; Davis, R. J.; Greenberg, M. E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270:1326-1331; 1995.
178. Yonish-Rouach, E.; Resnitzky, D.; Lotem, J.; Sachs, L.; Kimchi, A.; Oren, M. Wild-type p53 induces apoptosis in myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352:345-347; 1991.
179. Yuan, Z.-M.; Huang, Y.; Whang, Y.; Sawyers, C.; Weichselbaum, R.; Kharbanda, S.; Kufe, D. Role for c-Ab1 tyrosine kinase in growth arrest response to DNA damage. Nature 382:272-274; 1996.
180. Zhiying, L.; Otevrel, T.; Gao, Y.; Cheng, H.-E.; Seed, B.; Stamato, T. D.; Taccioli, G. E.; Alt, F. W. The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and VD(J) recombination. Cell 83:1079-1089; 1995.