The p53 gene as a modifier of intrinsic radiosensitivity: Implications for radiotherapy

Radiotherapy and Oncology

Volumn 40, Issue 3, 1996, Pages 197-223

  Bristow, Robert G ^a,b   Benchimol, Samuel ^b   Hill, Richard P ^a,b  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

Apoptosis; Cell cycle arrest; DNA repair; Genetic instability; p53; Radiosensitivity

Indexed keywords

PROTEIN P53; RETINOBLASTOMA PROTEIN;

CELL CYCLE G1 PHASE; DNA DAMAGE; DNA REPAIR; GENE THERAPY; HUMAN; IONIZING RADIATION; PRIORITY JOURNAL; RADIATION CARCINOGENESIS; RADIOSENSITIVITY; REVIEW; TUMOR SUPPRESSOR GENE;

EID: 0030232710     PISSN: 01678140     EISSN: None     Source Type: Journal    
DOI: 10.1016/0167-8140(96)01806-3     Document Type: Review

References (298)

1. [1] Abrahams, P., Schouten, R., van Laar, T., Houweling, A., Terleth, C. and van der Eb, A. Different regulation of p53 stability in UV-irradiated normal and DNA repair-deficient human cells. Mutat. Res. 336: 169-180, 1995.
2. 1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc. Natl. Acad. Sci. USA 92: 8493-8497, 1995.
3. [3] Ahomadegbe, J., Barrois, M., Fogel, S., Le Bian, M., Douc-Rasey, S., Duvillard, P., Armand, J. and Riou, G. High incidence of p53 alterations (mutation, deletion, overexpression) in head and neck primary tumours and metastases; absence of correlation with clinical outcome. Oncogene 10: 1217-1227, 1995.
4. [4] Aldridge, D.R., Arends, M.J. and Radford, I.R. 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 71: 571-577, 1995.
5. [5] Allam, A., Gioioso, D., Taghian, A., Duffy, M., Fidler, I. and Suit, H. Intrinsic radiation sensitivity: no correlation with the metastatic potential of human and marine tumor cell lines. J. Natl. Cancer Inst. 85: 1954-1957, 1993.
6. [6] Allalunis-Turner, J., Lintott, L.G., Barron, G.M., Day III, R.S. and Lees-Miller, S.P. Lack of correlation between DNA-dependent protein kinase activity and tumor cell radiosensitivity. Cancer Res. 55: 5200-5202, 1995.
7. 2 arrest-dependent immunoglobulin κ light chain gene expression. EMBO J. 14: 1392-1401, 1994.
8. [8] Arlett, C.F., Green, M.H.L., Priestley, A., Harcourt, S.A. and Mayne, L.V. Comparative human cellular radiosensitivity. I. The effect of SV40 transformation and immortalisation on the gamma-irradiation survival of skin derived fibroblasts from normal individuals and from ataxia-telangiectasia patients and heterozygotes. Int. J. Radiat. Biol. 54: 911-928, 1988.
9. [9] Artuso, M., Asuncion, E., Brésil, H., Vuillaume, M. and Hall, J. The role of the ataxia telangiectasia gene in the p53, WAF1/CIP1 (p21)-and GADD45-mediated response to DNA damage produced by ionising radiation. Oncogene 11: 1427-1435, 1995.
10. [10] Awwad, S., Jaros, E., Somes, J. and Lunec, J. p53 overexpression in head and neck carcinoma and radiotherapy results. Int. J. Radiat. Oncol. Biol. Phys. 34: 323-332, 1996.
11. [11] Bae, I., Smith, M.L., Sheikh, M.S., Zhan, Q., Scudiero, D.A., Friend, S.H., O'Connor, P.M. and Fornace, Jr. A.J. An abnormality in the p53 pathway following γ-irradiation in many wild-type p53 human melanoma lines. Cancer Res. 56: 840-847, 1996.
12. [12] Bakalkin, G., Yakovleva, T., Selivanova, G., Magnusson, K.P., Szekely, L., Kiseleva, E., Klein, G., Terenius, L. and Wiman, K.G. p53 binds single-stranded DNA ends and catalyzes DNA renaturation and strand transfer. Proc. Natl. Acad. Sci, USA 91: 413-417, 1994.
13. [13] Balcer-Kubiczek, E.K., Yin, J., Lin, K., Harrison, G.H., Abraham, J.M. and Meltzer, S.J. p53 mutational status and survival of human breast cancer MCF-7 cell variants after exposure to X-rays or fission neutrons. Radiat. Res. 142: 256-262, 1995.
14. [14] Bergh, J., Norberg, T., Sjögren, S., Lindgren, A. and Holmberg, L. Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy. Nat. Med. 11: 1029-1034, 1995.
15. [15] Biard, D.S.F., Martin, M., Le Rhun, A., Duthu, J., Lefaix, L., May, E. and May, P. Concomitant p53 gene mutation and increased radiosensitivity in rat lung embryo epithelial cells during neoplastic development. Cancer Res. 54: 3361-3364, 1994.
16. [16] Birrell, G.W. and Ramsay, J.R. Induction of p53 protein by gamma radiation in lymphocyte lines from breast cancer and ataxia telangiectasia patients. Br. J. Cancer 72: 1096-1101, 1995.
17. [17] Blondal, J. and Benchimol, S. The p53 gene in tumour progression. Semin. Cancer Biol. 5: 177-186, 1994.
18. [18] Bogue, M.A., Chengming, Zhu, Aguilar-Cordova, E., Donehower, L.A. and Roth D.B. p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. Genes Dev. 10: 5553-5645, 1996.
19. [19] Bouffer, S.D., Kemp, C.J., Balmain, A. and Cox, R. Spontaneous and ionizing radiation-induced chromosomal abnormalities in p53-deficient mice. Cancer Res. 55: 3883-3889, 1995.
20. [20] Bourhis, J., Bosq, J., Wilson, G., Bressac, B., Talbot, M., Levidat, A., Dondale, R., Jarin, N., Armend, J. and Lubaisch, B. Correlations between p53 gene expression and tumour-cell proliferation in oropharyngeal cancer. Int. J. Cancer 57: 458-462, 1994.
21. [21] Bracey, T.S., Miller, J.C., Preece, A. and Paraskeva, C. 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, 1995.
22. [22] Brachman, D., Beckett, M., Graves, D., Haraf, D., Yokes, E. and Weichselbaum, R. p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res. 53: 3667-3668, 1993.
23. [23] Braithwaite, A.W., Sturzbecher, H.-W., Addison, C., Palmer, C., Rudge, K. and Jenkins, J.R. Mouse p53 inhibits SV40 origin-dependent DNA replication. Nature 329: 458-460, 1987.
24. [24] Bristow, R.G, and Hill, R.P. Comparison between in vitro radiosensitivity and in vivo radioresponse of murine tumor cell lines. Part II. In vivo radioresponse following fractionated treatment and in vitro/ in vivo correlations. Int. J. Radiat. Oncol. Biol. Phys. 18: 331-345, 1990.
25. [25] Bristow, R.G., Jang, A., Peacock, J., Chung, S., Benchimol, S. and Hill, R.P. Mutant p53 increases radioresistance in rat embryo ribroblasts simultaneously transfected with HPV16-E7 and/or activated H-ras. Oncogene 9: 1527-1536, 1994.
26. [26] Bristow, R.G., Brail, L., Jang, A., Peacock, J., Chung, S., Benchimol, S. and Hill, R.P. p53-mediated radioresistance does not correlate with metastatic potential in tumorigenic rat embryo cell lines following oncogene transfection. Int. J. Radiat. Oncol. Biol. Phys. 34: 341-355, 1996.
27. [27] Bush, C. and McMillan, T.J. Micronucleus formation in human tumour cells: lack of correlation with radiosensitivity. Br. J. Cancer 67: 102-106, 1993.
28. [28] Butz, K., Shahabeddin, L., Geisen, C., Spitkovsky, D., Ullmann, A. and Hoppe-Seyler, F. Functional p53 protein in human papillomavirus-positive cancer cells. Oncogene 10: 927-936, 1995.
29. [29] Gaelics, C., Hemberg, A. and Karin, M. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 370: 220-223, 1994.
30. [30] Camplejohn, R.S., Perry, P., Hodgson, S.V., Turner, G., Williams, A., Upton, C., MacGeoch, C., Mohammed, S. and Barnes, D.M. A possible screening test for inherited p53-related defects based on the apoptotic response of peripheral blood lymphocytes to DNA damage. Br. J. Cancer 72: 654-662, 1995.
31. 1 cell cycle checkpoint pathway and ataxia-telangiectasia. Cancer Res. 54: 5054-5068.
32. [32] Canman, C.E., Gnber, T., Coutts, S. and Kastan, M.B. Growth factor modultion of p53-mediated growth arrest versus apoptosis. Genes Dev. 9: 600-611, 1995.
33. [33] Cassoni, A.M., McMillan, T.J., Peacock, J.H. and Steel, G.G. Differences in the level of DNA double-strand breaks in human tumour cell lines following low-dose-rate irradiation. Eur. J. Cancer 28: 1610-1614, 1992.
34. [34] Chang, E., Pirollo, K., Zou, Z., Cheung, H., Lawler, E., Garner, R., White, E., Bernstein, W., Fraumeni, J. and Blatner, W. Oncogenes in radioresistant, noncancerous skin fibroblasts from a cancer prone family. Science 237: 1036-1038, 1992.
35. [35] Chen, C.H., Zhang, J. and Ling, C.C. Transfected c-myc and c-Ha-ras modulated radiation-induced apoptosis in rat embryo cells. Radiat. Res. 139: 307-315, 1994.
36. [36] Chen, C.-Y., Oliner, J.D., Zhan, Q., Fornace, Jr. J.J., Vogelstein, B. and Kastan, M.B. Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway. Proc. Natl. Acad. Sci. USA 91: 2684-2688, 1994.
37. [37] Chen, Y., Chen, P.L. and Lee, W.H. Hot-spot p53 mutants interact specifically with two cellular proteins during progression of the cell cycle. Mol. Cell. Biol. 14: 6764-6772, 1994.
38. [38] Cho, U. Gorina, S., Jeffrey, P.D. and Pavletich, K.P. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265: 346-355, 1994.
39. [39] Cirielli, C., Riccioni, T., Yang, C., Pili, R., Gloe, T., Chang, J., Inyaku, K., Passaniti, A. and Capogrossi, M. C. Adenovirus-mediated gene transfer of wild-type p53 results in melanoma cell apoptosis in vitro and in vivo. Int. J. Cancer 63: 673-679, 1995.
40. [40] Clarke, A.R., Purdie, C., Harrison, D., Morris, R., Bird, C.C., Hogue, M. and Wyllie, A.H. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362: 849-852, 1993.
41. [41] Clarke, A.R., Gledhill, S., Hooper, M.L., Bird, C.C. and Wyllie, A.H. p53 dependence of early apoptotic and proliferative responses within the mouse intestinal epithelium following γ-irradiation. Oncogene 9: 1767-1773, 1994.
42. [42] Clore, G.M., Omichinski, J.G., Sakaguchi, K., Zambrano, M., Sakamoto, H., Appella, E. and Gronenborn, A.M. High-resolution structure of the oligomerization domain of p53 by multidimensional NMR. Science 265: 386-391, 1994.
43. [43] Cooper, J., Fu, K., Marks, J. and Silverman, J. Late effects of radiation therapy in the head and neck region. Int. J. Radiat. Oncol. Biol. Phys. 30: 575-581, 1994.
44. [44] Cox, L.S., Midgley, C.A. and Lane, D.P. Xenopus p53 is biochemically similar to the human tumour suppressor protein p53 and is induced upon DNA damage in somatic cells. Oncogene 9: 2951-2959, 1994.
45. [45] Cox, L.S., Hupp, T., Midgley, C.A. and Lane, D.P. A direct effect of activated human p53 on nuclear DNA replication. EMBO J. 14: 2099-2105, 1995.
46. [46] Cox, L.S. and Lane, D.P. Tumour suppressors, kinases and clamps: how p53 regulates the cell cycle in response to DNA damage. BioEssays 17: 501-507, 1995.
47. [47] Crook, T., Marston, N.J., Sara, E.A. and Vousden, K.H. Transcriptional activation by p53 correlates with suppression of growth but not transformation. Cell 79: 817-827, 1994.
48. [48] Cross, S.A. et al. A p53-dependent mitotic spindle checkpoint. Science 267: 1353-1356, 1995.
49. [49] Dameron, K., Volpert, O., Tainsky, M. and Bouck, N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265: 1582-1584, 1991.
50. [50] Deacon, J., Peckam, M. and Steel, G.G. The radioresponsiveness of human tumours and the initial slope of the cell survival curve. Radiotherapy and Oncology 2: 317-323, 1984.
51. [51] Demers, G.W., Foster, S.A., Halbert, C.L. and Galloway, D.A. Growth arrest by induction of p53 in DNA damaged keratinocytes is bypassed by human papillomavirus 16 E7. Proc. Natl. Acad. Sci. USA 91: 4382-4386, 1994.
52. WAF1/CIP1 undergo normal development, but are defective in G1 checkpoint control. Cell 82: 657-684, 1995.
53. [53] Dewey, W.C., Ling, C.C. and Meyn, R. Radiation-induced apoptosis: relevance to radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 33: 781-796, 1995.
54. [54] DiLeonardo, A., Linke, S.P., Yin, Y. and Wahl, G.M. Cell cycle regulation of gene amplification. Cold Spring Harbor Symposia in Quantitative Biology LVIII: 655-667, 1993.
55. [55] DiLeonardo, A., Linke, S.P., Charkin, K. and Wahl, G.M. DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev. 8: 2540-2551, 1994.
56. [56] Diller, L., Kassel, J., Nelson, C.E., Gryka, M.A., Litwak, G., Gebhardt, M., Bressac, B., Ozturk, M., Baker, S.J., Vogelstein, B. and Friend, S.H. p53 functions as a cell cycle control protein in osteosarcomas. Mol. Cell. Biol. 10: 5772-5781, 1990.
57. [57] Dittmer, D., Pati, S., Zambetti, G., Chu, S., Teresky, A., Moore, M., Finlay, C. and Levine, A.J. Gain of function mutations in p53. Nat. Genet. 4: 42-45, 1993.
58. [58] Donehower, L.A., Harvey, M., Slagle, B.L., McArthur, M.J., Montgomery, Jr. C.A., Butel, J.S. and Bradley, A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356: 215-221, 1992.
59. [59] Donehower, L.A., Harvey, M., Vogel, H., McArthur, M.J., Montgomery, Jr. C.A., Park, S.H., Thompson, T., Ford, R.J. and Bradley, A. Effects of genetic background on tumorigenesis in p53-deficient mice. Mol. Carcinog. 14: 16-22, 1995.
60. [60] Dover, R., Jayarma, Y., Patel, K. and Chinery, R. p53 expression in cultured cells following radioisotope labelling. J. Cell Sci. 107: 1181-1184, 1994.
61. [61] Dowell, S. and Hall, P. The p53 tumour suppressor gene and tumour prognosis: is there a relationship? J. Pathol. 177: 221-224, 1995.
62. [62] Duchaud, E., Ridet, A., Stoppa-Lyonnet, D., Janin, N., Moustacchi, E. and Rosselli, F. Deregulated apoptosis in ataxia telangiectasia: association with clinical stigmata and radiosensitivity. Cancer Res. 56: 1400-1404, 1996.
63. [63] Dullić, V., Kaufmann, W.K., Wilson, S.J., Tisty, T.D., Lees, E., Harper, J.W., Elledge, S.J. and Reed, S.I. p53-Dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76: 1013-1023, 1994.
64. [64] Dutta, A., Ruppert, J.M., Aster, J.C. and Winchester, E. Inhibition of DNA replication factor RPA by p53. Nature 365: 79-82, 1993.
65. 1 arrest and apoptosis. Cancer Res. 54: 1169-1174, 1994.
66. [66] Ellis, N., Groder, J., Ye, T., Strangler, J., Lennon, D., Ciocci, S., Proytcheva, M. and German, J. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83: 655-666, 1995.
67. [67] Elledge, R.M. Assessing p53 status in breast cancer prognosis: where should you put the thermometer if you think your p53 is sick? J. Natl. Cancer Inst. 88: 141-143, 1996.
68. [68] Fan, S., El-Deiry, W. S., Bae, I., Freeman, J., Jondle, D., Bhatia, K., Fornace, Jr. A.J., Magrath, I., Kohn, K.W. and 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,
69. [69] Fan, S., Smith, M.L., Rivet, II, D.J., Duba, D., Zhan, Q., Kohn, K.W., Fornace, Jr. A.J. and O'Connor, P.M. Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. Cancer Res. 55: 1649-1654, 1995.
70. [70] Fertil, B. and Malaise, E. Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves. Int. J. Radiat. Oncol. Biol. Phys. 11: 1699-1707, 1985.
71. [71] Finlay, C.A. The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Mol. Cell. Biol. 13: 301-306, 1993.
72. [72] Fisher, C.J., Gillett, C.E., Vojtěsěk, B., Barnes, D.M. and Millis, R.R. Problems with p53 immunohistochemical staining: the effect of fixation and variation in the methods of evaluation. Br. J. Cancer 69: 26-31, 1994.
73. [73] Ford, J.M. and Hanawalt, P.C. Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in global DNA repair but exhibit normal transcription-coupled repair and enhanced UV resistance. Proc. Natl. Acad. Sci. USA 92: 8876-8880, 1995.
74. [74] Forrester, K., Lupold, S.E., Ott, V.L., Chay, C.H., Band, V., Wang, X.W. and Harris, C.C. Effects of p53 mutants on wild-type p53-mediated transactivation are cell type dependent. Oncogene 10: 2103-2111, 1995.
75. [75] Forrester, K., Ambs, S., Lupold, S.E., Kapust, R.B., Spillare, E.A., Weinberg, W.C., Felley-Bosco, E., Wang, X.W., Geller, D.A., Tzeng, E., Billiar, T.R. and Harris, C.C. Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild-type p53. Proc. Natl. Acad. Sci. USA 93: 2442-2447, 1996.
76. [76] Frebourg, R., Sadelain, M., Ng, Y.-S., Kassel, J. and Friend, S.H. Equal transcription of wild-type and mutant p53 using bicistronic vectors results in the wild-type phenotype. Cancer Res. 54: 878-881, 1994.
77. [77] Fritsche, M., Haessler, C. and Brandner, G. Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene 8: 307-318, 1993.
78. [78] Fujiwara, T., Grimm, E., Mukhopadhyay, T., Cai, D., Owen-Schaub, L. and Roth, J. A retroviral wild-type p53 expression vector penetrates human lung cancer spheroids and inhibits growth by inducing apoptosis. Cancer Res. 53: 4129-4133, 1993.
79. [79] Fujiwara, T., Cai, D.W., Georges, R.N., Mukhopadhyay, T., Grimm, E.A. and Roth, J.A. Therapeutic effect of a retroviral wild-type p53 expression vector in an orthotopic lung cancer model. J. Natl. Cancer Inst. 86: 1458-1462, 1994.
80. [80] Fukasawa, K., Choi, T., Kuriyama, R., Rulong, S. and Vande Woude, G.F. Abnormal centrosome amplification in the absence of p53. Science 271: 1744-1747, 1996.
81. [81] Furuta, Y., Shinohara, T., Sano, K., Nagashima, K., Inoue, K., Tanaka, K. and Inuyama, Y. Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses. Laryngoscope 101: 79-85, 1991.
82. [82] Gannon, J.V. and Lane, D.P. p53 and DNA polymerase a compete for binding to SV40 T antigen. Nature 329: 456-458, 1987.
83. [83] Gasparini, G., Bevilacqua, P., Bonoldi, E., Testolin, A., Boracchi, P., Guglielmi, R.B. and Pezzella, F. Predictive and prognostic markers in a series of patients with head and neck squamous cell invasive carcinoma treated with concurrent chemoradiation therapy. Clin. Cancer Res. 1: 1375-1383, 1995.
84. [84] Girinsky, T., Lubin, R., Pignon, J., Chavaudra, N., Gazeau, J., Dubray, B., Cosset, J., Socie, G. and Fertil, B. Predictive value of in vitro radiosensitivity parameters in head and neck cancers and cervical carcinomas: preliminary correlations with local control and overall survival. Int. J. Radiat. Oncol. Biol. Phys. 25: 3-7, 1992.
85. [85] Girinsky, T., Koumenis, C., Graeber, T., Peehl, D.M. and Giaccia, A. Attenuated response of p53 and p21 in primary cultures of human prostatic epithelial cells exposed to DNA-damaging agents. Cancer Res. 55: 3726-3731, 1995.
86. [86] Gomez-Manzano, C., Fueyo, J., Kyritsis, P., Steck, P.A., Roth, J.A., McDonnell, T.J., Steck, K.D., Levin, V.A. and Yung, W.K.A. Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res. 56: 694-699, 1996.
87. [87] Goukon, Y., Sasano, J., Nishihira, T., Nagura, H. and Mori, S. p53 Overexpression in human esophageal carcinoma: a correlation with tumor DNA ploidy and two parameter flow cytometric study. Anticancer Res. 14: 1305-1312, 1994.
88. [88] Graeber, T., Peterson, J., Tsai, W., Monica, K., Fornace, A. and Giaccia, A. Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol. Cell. Biol. 14: 6264-6277, 1994.
89. [89] Graeber, T., Osmanian, C., Jacks, T., Housman, D., Koch, C., Lowe, S. and Giaccia, A. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379: 88-91, 1996.
90. [90] Grant, M., Bruton, R., Byrd, P., Gallimore, P., Steele, J., Taylor, A. and Grant, R. Sensitivity to ionising radiation of transformed human cells containing ras genes. Oncogene 5: 1159-1164, 1991.
91. [91] Greenblatt, M.S., Bennett, W.P., Hollstein, M. and Harris, C.C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54: 4855-4878, 1994.
92. [92] Guillouf, C., Rosselli, F., Krishnaraju, K., Moustacchi, E., Hoffman, B. and Liebermann, D. A. p53 involvement in control of G2 exit of the cell cycle: role in DNA damage-induced apoptosis. Oncogene 10: 2263-2270, 1995.
93. 1-phase checkpoint. Radiat. Res. 145: 289-298, 1996.
94. [94] Gupta, R.K., Patel, K., Bodmer, W.F. and Bodmer, J.G. Mutation of p53 in primary biopsy material and cell lines from Hodgkin's disease. Proc. Natl. Acad. Sci. USA 90: 2817-2821, 1993.
95. [95] Haas-Kogan, D.A., Kogan, S.C., Levi, D., Dazin, P., T'Ang, A., Fung, Y.-K.T. and Israel, M.A. Inhibition of apoptosis by the retinoblastoma gene product. EMBO J. 14: 461-472, 1995.
96. [96] Hainaut, P. and Milner, J. Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res. 53, 4469-4473, 1993.
97. [97] Hall, P.A. and Lane, D.P. p53 in tumour pathology: can we trust immunohistochemistry? J. Pathol. 172: 1-4, 1994.
98. [98] Hann, B.C. and Lane, D.P. The dominating effect of mutant p53. Nat. Genet. 9: 221-222, 1995.
99. [99] Harper, J.W., Adami, G.R., Wei, N., Keyomarsi, K. and Elledge, S.J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805-816, 1993.
100. [100] Hartley, K.O., Cell, D., Smith, G.C.M., Zhan, H., Divecha, N., Connelly, M.A., Admon, A., Lees-Miller, S.P., Anderson, C.W. and Jackson, S.P. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell 82: 849-856, 1995.
101. [101] Hartwell, L. Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. Cell 71: 543-546, 1992.
102. [102] Harvey, M., Sands, A.T., Weiss, R.S., Hegi, M.E., Wiseman, R.W., Pantazis, P., Giovanella, B.C., Tainsky, M.A., Bradley, A. and Donehower, L.A. In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice. Oncogene 8: 2457-2467, 1993.
103. [103] Harvey, M., Vogel, H., Morris, D., Bradley, A., Bernstein, A. and Donehower, L.A. A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice. Nat, Genet. 9: 305-311, 1995.
104. [104] Hawkins, D.S., Demers, G.W. and Galloway, D.A. Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents. Cancer Res. 56: 892-898, 1996.
105. [105] Hermeking, H. and Eick, D. Mediation of c-myc-mediated apoptosis by P53. Science 265: 2091-2093, 1994.
106. [106] Hickman, A.W., Jaramillo, R.J., Lechner, J.F. and Johnson, N.F. α-particle-induced p53 protein expression in a rat lung epithelial cell strain. Cancer Res. 54: 5797-5800, 1994.
107. [107] Hickman, E.S., Picksley, S.M. and Vousden, K.H. Cells expressing HPV16 E7 continue cell cycle progression following DNA damage induce p53 activation. Oncogene 9: 2177-2181, 1994.
108. [108] Hill, R.P. Cellular basis of radiotherapy and experimental radiotherapy. In: The Basic Science of Oncology, pp. 259-301. Editors: I.F. Tannock and R.P. Hill. Pergamon Press, New York, 1992.
109. [109] Hockenbery, D.M., Oitvai, Z.N., Yin, X.-M., Milliman, C.L. and Korsmeyer, S.J. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75: 241-251, 1993.
110. [110] Hockenbery, D. Defining apoptosis. Am. J. Pathol. 146: 16-19, 1995.
111. [111] Hoeijmakers, J.H.J. Human nucleotide excision repair syndromes: molecular clues to unexpected intricacies. Eur. J. Cancer 30A: 1912-1921, 1994.
112. [112] Hoever, M., Clement, J., Wedleilo, D., Montenarch, M. and Knochel, N. Overexpression of wild type p53 interferes with normal development in Xenopus laevis embryos. Oncogene 9: 109-120, 1994.
113. [113] Hoffman, B. and Liebermann, D.A. Molecular controls of apoptosis: differentiation/growth arrest primary response genes, protooncogenes, and tumor suppressor genes as positive and negative modulators. Oncogene 9: 1807-1812, 1994.
114. [114] Hupp, T.R., Sparks, A. and Lane, D.P. Small peptides activate the latent sequence-specific DNA binding function of p53. Cell 83: 237-245, 1995.
115. [115] Hursting, S.D., Perkins, S.N., Haines, D.C., Ward, J.M. and Phang, J.M. Chemoprevention of spontaneous tumorigenesis in p53-knockout mice. Cancer Res. 55: 3949-3953, 1995.
116. [116] Isaacs, W.B., Carter, B.S. and Ewing, C.M. Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res. 51: 4716-4720, 1991.
117. [117] Ishizaki, K., Ejima, Y., Matsunaga, T., Hara, R., Sakamoto, A., Ikenaga, M., Ikawa, Y. and Aizawa, S. Increased UV-induced SCEs but normal repair of DNA damage in p53-deficient mouse cells. Int. J. Cancer 58: 254-257, 1994.
118. [118] Jansson, T., Inganäs, M., Sjögren, S., Torbjörn, N., Lindgren, A., Holmberg, L. and Bergh, J. p53 status predicts survival in breast cancer patients treated with or without postoperative radiotherapy: a novel hypothesis based on clinical findings. J. Clin. Oncol. 13: 2745-2751, 1995.
119. [119] Jayaraman, L. and Prives, C. Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus. Cell 81: 1021-1029, 1995.
120. [120] Johnson, P., Gray, D., Mowat, M. and Benchimol, S. Expression of wild-type p53 is not compatible with continued growth of p53-negative tumor cells. Mol. Cell. Biol. 11: 1-11, 1991.
121. [121] Johnson, M., Dimitrov, D., Vojta, P.J., Barrett, J.C., Noda, S., Pereira-Smith, O.M. and Smith, J.R. Evidence for a p53-independent pathway for upregulation of DSI1/CIP1/WAF1p21 RNA in human cells. Mol. Carcinog. 11: 59-64, 1994.
122. [122] Jonveaux, P. and Berger, R. Lack of mutations in the p53 gene exons 5 to 8 in ataxia-telangiectasia. Cancer Genet. Cytogenet. 66: 128-129, 1993.
123. [123] Jung, M., Notario, V. and Dritschilo, A. Mutations in the p53 gene in radiation-sensitive and -resistant human squamous carcinoma cells. Cancer Res. 52: 6390-6393, 1992.
124. [124] Jung, M. and Dritschilo, A. Modification of the radiosensitivity of human testicular cancer cells by Simian Virus 40 sequences. Radiat. Res. 140: 186-190, 1994.
125. [125] Kasid, U., Pirollo, K., Dritschilo, A. and Chang, E. Oncogenic basis of radiation resistance. Adv. Cancer Res. 61: 195-233, 1993.
126. [126] Kastan, M.B., Onyekwere, D., Sidransky, D., Vogelstein, B. and Craig, R. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51: 6304-6311, 1991.
127. [127] Kastan, M.B., Zhan, Q., El-Deiry, W., Carrier, F., Jacks, T., Walsh, W., Plunkett, B.S., Vogelstein, B. and Fornace, Jr. A.J. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71: 587-597, 1992.
128. [128] Katayose, D., Wersto, R., Cowan, K.H. and Seth, P. Effects of a recombinant adenovirus expressing WAF1/Cip1 on cell growth, cell cycle and apoptosis. Cell Growth Differ. 6: 1207-1212, 1995.
129. [129] Kawashima, K., Mihara, K., Usuki, J., Shimizu, N. and Namba, M. Transfected mutant p53 gene increases X-ray-induced cell killing and mutation in human fibroblasts immortalized with 4-nitroquinoline 1 -oxide but does not induce neoplastic transformation of the cells. Int. J. Cancer 61: 76-79, 1995.
130. [130] Kazontsev, A., Sancar, A., Kearsey, J., Shivji, M., Hall, P., Wood, R.D., Smith, M., Chen, I. and Fornace, A. Does the p53 upregulated Gadd45 protein have a role in excision repair? Science 270: 1003-1006, 1995.
131. Cip1. Oncogene 11: 1675-1683, 1995.
132. [132] Keiser, A., Weich, H., Brandner, G., Marme, D. and Kolch, W. Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene 9: 963-969, 1994.
133. [133] Kemp, C.J., Wheldon, T. and Balmain, A. p53-deficient mice are extremely susceptible to radiation-induced tumorigenesis. Nat. Genet. 8: 66-69, 1994.
134. [134] Kessis, T.D., Slebos, R.J., Nelson, W.G., Kastan, M.B., Plunkett, B.S., Han, S.M., Lorincz, A.T., Hedrick, L. and Cho, K.R. Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage. Proc. Natl. Acad. Sci. USA 90: 3988-3992, 1993.
135. [135] Khanna, K.K., Beamish, H., Yan, J., Hobson, K., Williams, R., Dunn, I. and Lavin, M.F. Nature of G1/S cell cycle checkpoint detect in ataxia-telangiectasia. Oncogene 11: 609-618, 1995.
136. [136] Kirchgessner, C.U., Paul, C.K., Evans, J.W., Cuomo, C.A., Fried, L.M., Carter, T., Oettinger, M.A, and Brown, M.J. DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267: 1178-1182, 1995.
137. [137] Kitada, S., Krajewski, S., Miyashita, T., Krajewska, M. and Reed, J.C. γ-Radiation induces upregulation of Bax protein and apoptosis in radiosensitive cells in vivo. Oncogene 12: 187-192, 1996.
138. [138] Klingelhutz, A.J., Foster, S.A. and McDougall, J.K. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 380: 79-82, 1996.
139. [139] Kovach, J.S., Hartmann, A., Blaszyk, J., Cunningham, J., Schaid, D. and Sommer, S.S. Mutation detection by highly sensitive methods indicates that p53 mutations in breast cancer can have important prognostic value. Proc. Natl. Acad. Sci. USA 93: 1093-1096, 1996.
140. [140] Kuerbitz, S.J., Plunkett, B.S., Walsh, W.V. and Kastan, M.B. Wildtype p53 is a cell cycle checkpoint determinant following irradiation. Proc. Natl. Acad. Sci. USA 89: 7491-7495, 1992.
141. [141] Kyritsis, A., Bondy, M., Hess, K., Cunningham, J., Zhu, D., Amos, C., Yung, W., Levin, V. and Bruner, J. Prognostic significance of p53 immunoreactivity in patients with glioma. Clin. Cancer Res. 1: 1617-1622, 1995
142. [142] Lane, D. and Benchimol, S. p53: oncogene or antioncogene? Genes Dev. 4: 1-8, 1990.
143. [143] Lane, D.P. and Crawford, L. T antigen is bound to a host protein in SV-40 transformed cells. Nature 278: 261-263, 1979.
144. [144] Langendijk, J.A., Thunnissen, F.B.J.M., Lamers, R.J.S., de Jong, J.M,A., ten Velde, G.P.M. and Wouters, E.F.M. The prognostic significance of accumulation of p53 protein in stage III non-small cell lung cancer treated by radiotherapy. Radiother. Oncol. 36: 218-224, 1995.
145. [145] Lee, J.M. and Bernstein, A. p53 mutations increase resistance to ionizing radiation. Proc. Natl. Acad. Sci. USA 90: 5742-5746, 1993.
146. [146] Lee, J.M., Abrahamson, J.L.A., Kandel, R., Donehower, L.A. and Bernstein, A. Susceptibility to radiation-carcinogenesis and accumulation of chromosomal breakage in p53-deficient mice. Oncogene 9: 3731-3736, 1994.
147. [147] Lee, S., Elenbass, B., Levine, A. and Griffith, J. p53 and its 14 kDa C-Terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell 81: 1013-1020, 1995.
148. [148] Lees-Miller, S., Chen, Y. and Anderson, C.W. Human cells contain a DNA-activated protein kinase that phosphorylates Simian Virus 40 T antigen, mouse p53 and the human Ku autoantigen. Mol. Cell. Biol. 10: 6472-6481, 1990.
149. [149] Leith, J.T. Correspondence re: D.G. Brachman et al. Mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res. 53: 3667-3669, 1993. (Letter to the Editor). Cancer Res. 54: 5021, 1994.
150. [149] Leith, J.T. Correspondence re: D.G. Brachman et al. Mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res. 53: 3667-3669, 1993. (Letter to the Editor). Cancer Res. 54: 5021, 1994.
151. [150] Lennon, S.V., Martin, S.J. and Cotter, T.G. Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell. Prolif. 24: 203-214, 1991.
152. 2 checkpoint response to ionizing radiation. Cancer Res. 55: 2500-2502, 1995.
153. [152] Leveillard, T., Andera, L., Bissonette, N., Schaeffer, L., Bracco, L., Egly, J. and Wasylyk, B. Functional intercations between p53 and the TFIIH complex are affected by tumour-associated muations. EMBO J. 15: 1615-1624, 1996.
154. [153] Levine, E.L., Renehan, A., Gossiel, R., Davidson, S.E., Roberts, S.A., Chadwick, C., Wilks, D.P., Potten, C.S., Hendry, J.H., Hunter, R.D. and West, C.M.L, Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma. Radiother. Oncol. 37: 1-9, 1995.
155. [154] Lewis, A., Mei, S., Doty, J., Chen, Y. and Pardo, F.S. Relationship between intrinsic radiation sensitivity and metastatic potential. Int. J. Radiat. Oncol. Biol. Phys. 34: 103-110, 1996.
156. [155] Li, Y., Jenkins, C.W., Nichols, M.A. and Xiong, U. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. Oncogene 9: 2261-2268, 1994.
157. 1 arrest in established human tumor cell lines. Oncogene 11: 1885-1892, 1995.
158. WAF1 gene activation. Mol. Cell. Biol. 16: 1786-1798, 1996.
159. 1 arrest, Mol. Cell. Biol. 15: 6045-6054, 1995.
160. [159] Ling, C.C., Chen, C.H. and Li, W.X. Apoptosis induced at different dose rates: implication for the shoulder region of cell survival curves. Radiother. Oncol. 32: 129-136, 1994.
161. [160] Linzer, D. and Levine, A.J. Characterization of a 54 kDa cellular SV40 tumour antigen present in SV40-transformed cells and untransfected embryonal carcinoma cells. Cell 17: 43-52, 1979.
162. [161] Lipponen, P.K. and Liukkonen, T.J. Reduced expression of retinoblastoma (Rb) gene protein is related to cell proliferation and prognosis in transitional-cell bladder cancer. J. Cancer Res. Clin. Oncol. 121: 44-50, 1995.
163. [162] Little, J.B. Changing views of cellular radiosensitivity (Failla Memorial Lecture). Radiat. Res. 140: 299-311, 1994.
164. [163] Liu, R.J., El-Naggar, A.K., McDonnell, T.J., Steck, K.D., Wang, M., Taylor, D.L. and Clayman, G.L. Apoptosis induction mediated by wild-type p53 adenoviral gene transfer in squamous cell carcinoma of the head and neck. Cancer Res. 55: 3117-3122, 1995.
165. [164] Liu, Y., Mertindale, J., Gorospe, M. and Holbrook, N. Regulation of p21WAF1/CIP1 expression through mitogen-activated protein kinase signaling pathway. Cancer Res. 56: 31-35, 1996.
166. [165] Livingstone, L., White, J., Sprouse, E., Livanos, E., Jacks, T. and Tlsty, T. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70: 923-935, 1992.
167. [166] Lowe, S.W., Schmitt, E.M., Smith, S.W., Osborne, B.A. and Jack, T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362: 847-852, 1993.
168. [167] Lowe, S.W., Ruley, H.E., Jacks, T. and Housman, D.E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74: 957-967, 1994.
169. [168] Lowe, S.W., Jacks, T., Housman, D.E. and Ruley, J.E. Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. Proc. Natl. Acad. Sci. USA 91: 2026-2030, 1994.
170. [169] Lowe, S.W., Bodis, S., McClatchey, A., Fisher, D., Jacks, T. and Housman, D. P53 status and the efficacy of cancer therapy in vivo. Science 266: 807-810, 1994.
171. [170] Lu, X., Park, S., Thompson, T. and Lane, D.P. Ras-induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation. Cell 70: 153-161, 1992.
172. [171] Lu, X. and Lane, D.P. Differential induction of transcriptionally active p53 following UV or ionizing radiation: defects in chromosomal instability syndromes? Cell 75: 765-778, 1993.
173. [172] Lücke-Huhle, C. Alterations in oncogene expression and radiosensitivity in the most frequently used SV40-transformed human skin fibroblasts. Int. J. Radiat. Biol. 65: 665-673, 1994.
174. [173] Ludlow, J., Howell, R. and Smith, H. Hypoxic stress induces reversible hypophosphorylation of pRB and reduction in cyclin A abundance independent of cell cycle progression. Oncogene 8: 331-339, 1993.
175. [174] Macgeoch, C., Barnes, D.M., Newton, J.A., Mohammed, S.A., Hodgson, S.V., Ng, M., Bishop, D.T. and Spurr, N.K. p53 protein detected by immunohistochemical staining is not always mutant. Dis. Markers 11: 239-250, 1993.
176. [175] Macleod, K.F., Sherry, N., Hannon, G., Beach, D., Tokino, T., Kinzler, K., Vogelstein, B. and Jacks, T. p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev. 9: 935-944, 1995.
177. [176] Maity, A., McKenna, W.G. and Muschel, R.J. The molecular basis for cell cycle delays following ionizing radiation: a review. Radiother. Oncol. 31: 1-13, 1994.
178. [177] Malkin, D., Li, F., Strong, L., Fraumeni, J., Nelson, C., Kim, D., Kassel, J., Gryka, M., Bischoff, F., Tainsky, M. and Friend, S. Germline p53 mutations in a familial syndrome of breast cancer, sarcoma and other neoplasms. Science 250: 1233-1238, 1990.
179. [178] Maltzman, W. and Czyzyk, K. UV-irradiation stimulates levels of p53 cellular tumour antigen in nontransformed mouse cells. Mol. Cell. Biol. 4: 1689-1694, 1984.
180. [179] Maxwell, S.A. and Roth, J.A. Post-translational regulation of p53 tumor suppressor protein function. Crit. Rev. Oncog. 5: 23-57, 1994.
181. [180] McIlwrath, A.J.,Vasey, P.A., Ross, G.M. and 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.
182. [181] McKenna, W., Weiss, M., Endlich, B., Ling, C., Bakanauskas, M., Kelsten, M. and Muschel, R. Synergistic effect of the v-myc oncogene with H-ras on radioresistance. Cancer Res. 50: 97-102, 1990.
183. [182] McMillan, T.J. and Peacock, J.H. Molecular determinants of radiosensitivity in mammalian cells. Int. J. Radiat. Biol. 65: 49-55, 1994.
184. [183] McWhir, J., Selfridge, J., Harrison, D.J., Squires, S. and Melton, D.W. Mice with DNA repair gene (ERCC-I) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Nat. Genet. 5: 217-223, 1993.
185. [184] Merritt, A.J., Potten, C.S., Kemp, C.J., Hickman, J.A., Balmain, A., Lane, D.P. and 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.
186. [185] Meyn, M., Strasfeld, L. and Allen, C. Testing the role of p53 in the expression of gentic instability and apoptosis in ataxia-telangiectasia. Int. J. Radiat. Biol. 66: 141-149, 1994
187. [186] Meyn, R.E., Stephens, L.C., Ang, K.K., Hunter, N.R., Brock, W.A., Milas, L. and Peters, L.J. Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies. Int. J. Radiat. Biol. 64: 583-591, 1993.
188. [187] Meyn, R.E., Stephens, L.C., Hunter, N.R., Ang, K.K. and Milas, L. Reemergence of apoptotic cells between fractionated doses in irradiated murine tumors. Int. J. Radiat. Oncol. Biol. Phys. 30: 619-624, 1994.
189. [188] Michieli, P., Chedid, M., Lin, D., Pierce, J.H., Mercer, W.E. and Givol, D. Induction of WAF1/CIP1 by a p53-independent pathway. Cancer Res. 54: 3391-3395, 1994.
190. [189] Midgley, C.A., Owens, B., Briscoe, C.V., Thomas, D.B., Lane, D.P. and Hall, P.A. Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo. J. Cell Sci. 106: 1843-1848, 1995.
191. [190] Milner, J. Forms and functions of p53. Semin. Cancer Biol. 5: 211-219, 1994.
192. [191] Milner, J. DNA damage, p53 and anticancer therapies. Nat. Med. 1: 879-881, 1995.
193. [192] Mirzayans, R., Aubin, R.A., Bosnich, W., Blattner, W.A. and Paterson, M.C. Abnormal pattern of post-γ-ray DNA replication in radioresistant fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome. Br. J. Cancer 71: 1221-1230, 1995.
194. [193] Miyashita, T. and Reed, J.C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80: 293-299, 1995.
195. [194] Moll, U.M., LaQuaglia, M., Bénard, J. and Riou, G. Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors. Proc. Natl. Acad. Sci. USA 92: 4407-4411, 1995.
196. 1 checkpoint after DNA damage. Mol. Cell, Biol. 16: 1126-1137, 1996.
197. [196] Momand, J., Zambetti, G.P., Olson. D.C., George, D. and Levine, A.J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69: 1237-1245, 1992.
198. [197] Morgan, W.F. and Murnane, J.P. A role for genomic instability in cellular radioresistance? Cancer Metastasis Rev. 14: 49-58, 1995.
199. [198] Mukhopadhyay, D., Tsiokas, L. and Sukhatme, V.P. Wild-type p53 and v-Src exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res. 55: 6161-6165, 1995.
200. [199] Muschel, R.J., Bernhard, E.J., Garza, L., McKenna, W.G. and 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.
201. 2/M delay and cellular radiosensitivity. Int. J. Radiat. Biol. 66: 373-379, 1994.
202. [201] Nakano, T., Oka, K. and Taniguchi, N. Manganese superoxide dismuatse expression correlates with p53 status and local recurrance of cervical carcinoma with radiation therapy. Cancer Res. 56: 2771-2775, 1996
203. 1 arrest is selectively mediated by the p53-WAF1 /CIP1 pathway in human thyroid cells. Cancer Res. 55: 2075-2080, 1995.
204. [203] Nelson, W.G. and Kastan, M.B. DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways. Mol. Cell. Biol. 14: 1815-1823, 1994.
205. + T cells. Proc. Natl. Acad. Sci. USA 91: 3171-3175, 1994.
206. [205] Oberosler, P., Hloch, P., Ramsperger, U. and Stahl, H. p53-catalyzed annealing of complementary single-stranded nucleic acids. EMBO J. 12: 2389-2396, 1993.
207. [206] O'Connor, P.M., Jackman, J., Jondle, D., Bhatia, K., Magrath, I. and Kohn, K.W. Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitts lymphoma cell lines. Cancer Res. 53: 4776-4780, 1993.
208. [207] Olive, P.L., Banáth, J.P. and MacPhail, H.S. Lack of a correlation between radiosensitivity and DNA double-strand break induction or rejoining in six human tumor cell lines. Cancer Res. 54: 3939-3946, 1994.
209. [208] Olson, D.C. and Levine, A.J. The properties of p53 proteins selected for the loss of suppression of transformation. Cell Growth Differ. 5: 61-71, 1994.
210. [209] Ory, K., Legros, Y., Auguin, C. and Soussi, T. Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation. EMRO J. 13: 3496-3504, 1994.
211. [210] Pardo, F.S., Bristow, R.G., Hunt, T. and Borek, C. Role of transfection and clonal selection in mediating radioresistance. Proc. Natl. Acad. Sci. USA 88: 10652-10656, 1990.
212. [211] Pardo, F.S., Su, M., Borek, C., Preffer, F., Dombkowski, D., Gerweck, L. and Schmidt, E.V. Transfection of rat embryo cells with mutant p53 increases the intrinsic radiation resistance. Radiat. Res. 140: 180-185, 1994.
213. [212] Park, D.J., Nakamura, H., Chumakov, A.M., Said, J.W., Miller, C.W., Chen, D.L. and Koeffler, H.P. Transactivational and DNA binding abilities of endogenous p53 in p53 mutant cell lines. Oncogene 9: 1899-1906, 1994.
214. 2-phase X-irradiation in relation to DNA repair and radiosensitivity in a cancer-prone family with Li-Fraumeni Syndrome. Radiat. Res. 136: 236-240., 1993.
215. [214] Peacock, J., Matlashewski, G. and Benchimol, S. Synergism between pairs of immortalizing genes in transformation assays of rat embryo fibroblasts. Oncogene 2: 1769-1774, 1990.
216. [215] Peacock, J.W. and Benchimol, S. Mutation of the endogenous p53 gene in cells transformed by HPV-16 E7 and EJ c-ras confers a growth advantage involving an autocrine mechanism. EMBO J. 13: 1084-1092, 1994.
217. 1 checkpoint is retained in tumorigenic rat embryo fibroblast clones transformed by the human papillomavirus type 16 E7 gene and EJ-ras. Mol. Cell. Biol. 15: 1446-1454, 1995.
218. [217] Pocard, M., Chevillard, S.,Villaudy, J., Poupon, M.F., Butrillaux, B. and Remvikos, Y. Different p53 mutations produce distinct effects on the ability of colon carcinoma cells to become blocked at the G1/S boundary after irradiation. Oncogene 12: 875-882, 1996.
219. [218] Poljak, M. and Cerar, A. Human papillomavirus type 16 DNA in oesophageal squamous cell carcinoma. Anticancer Res. 13: 2113-2116, 1993.
220. 2 delay. Cancer Res. 55: 1643-1648, 1995.
221. [220] Prendergast, N., Atkins, M., Schatte, E., Paulson, D. and Walther, P. p53 immunohistochemical and genetic alterations are associated at high incidence with post-irradiated locally persistent prostate carcinoma. J. Urol. 155: 1685-1692, 1996.
222. [221] Radford, I.R. p53 status, DNA double-strand break repair proficiency, and radiation response of mouse lymphoid and myeloid cell lines. Int. J. Radiat. Biol. 66: 557-560, 1994.
223. 6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent. Oncogene 12: 693-697, 1006.
224. [223] Reed, M., Woelker, B., Wang, P., Wang, Y., Anderson, M.E. and Tegtmyer, P. The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation. Proc. Natl. Acad. Sci. USA 92: 9455-9459, 1995.
225. [224] Renzing, J. and Lane, D.P. p53-dependent growth arrest following calcium phosphate-mediated transfection of murine fibroblasts. Oncogene 10: 1865-1868, 1995.
226. [225] Rolley, N., Butcher, S. and Milner, J. Specific DNA binding by different classes of human p53 mutants. Oncogene 11: 763-770, 1995.
227. [226] Roselli, F., Ridet, A., Soussi, T., Duchaud, E., Alapetitle, C. and Moustacchi, E. p53-dependent pathway of radiation-induced apoptosis is altered in Fanconi anemia. Oncogene 10: 9-17, 1995.
228. [227] Rotter, V., Schwartz, D., Almon, E., Goldfinger, N., Kapon, A., Meshorer, A., Donehower, L.A. and Levine, A.J. Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome. Proc. Natl. Acad. Sci. USA 90: 9075-9079, 1993.
229. [228] Rovinski, B. and Benchimol, S. Immortalization of rat embryo fibroblasts by the cellular p53 oncogene. Oncogene 2: 445-452, 1988.
230. 1 checkpoint-competent cells. Cancer Res. 55: 1639-1642, 1995.
231. [230] Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, A.A., Smith, S., Uziel, T., Sfez, S., Ashkenazi, M., Pecker, I., Frydman, M., Harnick, 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., Taylor, A.M.R., Arlett, C.F., Miki, T., Weissman, S.M., Lovett, M., Collins, F.S. and Shiloh, Y. A single ataxia telangiectasia gene with a product similar to P1-3 kinase. Science 268: 1749-1753, 1995.
232. [231] Schneffner, M., Werness, B., Huibregtse, J., Levine, A.J. and Howley, P. The E oncoprotein encoded by human papilomavirus types 16 and 18 promotes the degradation of p53. Cell 63: 1129-1136, 1990.
233. [232] Schwartz, J.L. The role of constitutive and inducible processes in the response of human squamous cell carcinoma cell lines to ionizing radiation. Radiat. Res. 138: 37-39, 1994.
234. [233] Shin, D., Lee. J., Lippman, S., Lee, J., Tu, N., Choi, G., Heyne, K., Shin, H., Ro, J., Goepfert, H., Hong, W. and Hittelman, W. p53 Expression: predicting recurrance amd second primary tumors in head and neck squamous cell carcinoma. J. Natl. Cancer Inst. 88: 519-529, 1996
235. [234] Sidransky, D., Mikkelsen, T., Schwechheimer, K., Roseblum, M.L., Cavanee, W. and Vogelstein, B. Clonal expansion of p53 mutant cells in associated with brain tumour progression. Nature 355: 846-847, 1992.
236. [235] Siegel. J., Fritsche, M., Mai, S., Brandner, G. and Hess, R.D. Enhanced p53 activity and accumulation in response to DNA damage upon DNA transfection. Oncogene 11: 1363-1370, 1995.
237. [236] Siles, E., Villalobos, M., Valenzuela, M.T., Núñez, M.I., Gordon, A., McMillan, T.J., Pedraza, V. and Ruiz de Almodóvar, J.M. Relationship between p53 status and radiosensitivity in human tumor cell lines. Br. J. Cancer 73: 581-588, 1996.
238. [237] Sjögren, S., Inganäs, M., Norberg, T., Lindgren, A., Nordgren, H., Holmberg, L. and Berg, J. The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry. J. Natl. Cancer Inst. 88: 173-182, 1996.
239. 1 arrest involves pRB-related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein. Proc. Natl. Acad. Sci. USA 91: 5320-5324, 1994.
240. 1 checkpoint does not decrease cell survival following DNA damage. Cancer Res. 53, 4164-4168, 1993.
241. [240] Slingerland, J.M., Jenkins, J.R. and Benchimol, S. The transforming and suppressor functions of p53 alleles: effects of mutations that disrupt phosphorylation, oligomerization and nuclear translocation. EMBO J. 12: 1029-1037, 1993.
242. [241] Slootweg, P.J., Koole, R. and Hordijk, G.J. The presence of p53 protein in relation to Ki-67 as cellular proliferation marker in head and neck squamous cell carcinoma and adjacent dysplastic mucosa. Oral Oncol. Eur. J. Cancer 30: 138-141, 1994.
243. 2 blocks, cyclin B expression and cdc2 expression in human squamous carcinoma cell lines with different radiosensitivities. Radiother. Oncol. 33: 217-227, 1994.
244. [243] Smith, M.L., Zhan, Q., Bae, I. and Fornace, Jr. A.J. Role of retinoblastoma gene product in p53-mediated DNA damage response. Exp. Cell Res. 215: 386-389, 1994.
245. [244] Smith, M.L., Chen, I.-T., Zhan, Q., Bae, I., Chen, C.Y., Gilmer, T.M., Kastan, M.B., O'Connor, P.M. and Fornace, Jr. A.J. Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science 266: 1376-1380, 1994.
246. [245] Smith, M.L., Chen, I-T., Zhan, Q., O'Connor, P.M. and Fornace, Jr. A.J. Involvement of the p53 tumor suppressor in repair of UV-type DNA damage. Oncogene 10: 1053-1059, 1995.
247. [246] Srivastava, S., Wang, S., Tong, Y.A., Hao, Z.-M. and Chang, E.H. Dominant negative effect of a germ-line mutant p53: a step fostering tumorigenesis. Cancer Res. 53: 4452-4455, 1993.
248. [247] Srivastava, S., Wang, S., Tong, Y.A., Pirollo, K. and Chang, E.H. Several mutant p53 proteins detected in cancer-prone families with Li-Fraumeni syndrome exhibit transdominant effects on the biochemical properties of the wild-type p53. Oncogene 8: 2449-2456, 1993.
249. [248] Stapper, N.J., Stuschke, M., Sak, A. and Stüben, G. Radiation-induced apoptosis in human sarcoma and glioma cell lines. Int. J. Cancer 62: 58-62, 1995.
250. [249] Staunton, M.J. and Gaffney, E.F. Tumor type is a determinant of susceptibility to apoptosis. Am. J. Clin. Pathol. 103: 300-307, 1995.
251. [250] Stephens, L.C., Ang, K.K., Schultheiss, T.E., Milas, L. and Meyn, R.E. Apoptosis in irradiated murine tumor. Radiat. Res. 127: 308-316, 1991.
252. [251] Stewart, N., Hicks, G.G., Paraskevas, F. and Mowat, M. Evidence for a second cell cycle block at G2/M by p53. Oncogene 10: 109-115, 1995.
253. [252] Strasser, A., Harris, A.W., Jacks, T. and Cory, Z. DNA damage can induce apoptosis in proliferating lymphoid cells via p53-independent mechanisms inhibitable by Bcl-2. Cell 79: 329-339, 1994.
254. [253] Sturzbecher, H., Donzelmann, B., Henning, W., Knippschild, U. and Buchhop, S. p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction. EMBO J. 15: 1992-2002, 1996.
255. [254] Su, L.-N. and Little, J.B. Transformation and radiosensitivity of human diploid skin fibroblasts transfected with SV40 T-antigen mutants defective in RB and p53 binding domains. Int. J. Radiat. Biol. 62: 461-468, 1992.
256. [255] Suit, H. Local control and patient survival. Int. J. Radiat. Oncol. Biol. Phys. 23: 653-660, 1992.
257. [256] Suit, J., Allam, A., Allalunis-Turner, J., Brock, W., Girinsky, T., Hill, S., Hunter, N., Milas, L., Pearcey, R., Peters, L., Welch, D.R., West, C. and Efird, J. Is tumor cell radiation resistance correlated with metastatic ability? Cancer Res. 54: 1736-1741, 1994.
258. [257] Symonds, H., Krall, L., Remington, L., Saenz-Robles, M., Lowe, S., Jacks, T. and Van Dyke, T. p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 78: 703-711, 1994.
259. [258] Szekely, L., Selivanova, G., Magnusson, K.P., Klein, G. and Wiman, K.G. EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins. Proc. Natl. Acad. Sci. USA 90: 5455-5459, 1993.
260. [259] Thacker, J. Cellular radiosensitivity in ataxia-telangiectasia. Int. J. Radiat. Biol. 66: 87-96, 1994.
261. II60. Science 267: 100-103, 1995.
262. [261] Tishler, R.B., Calderwood, S.K., Coleman, C.N. and Price, B.D. Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents. Cancer Res. 53: 2212-2216, 1993.
263. [262] Tsang, N.-M. and Little, J.B. Effect of restoration of retinoblastoma gene function on the radiosensitivity of cells of human tumor cell lines. Radiat. Res. 140: 172-179, 1994.
264. [263] Tsang, N.-M., Nagasawa, H., Li, C. and Little, J.B. Abrogation of p53 function by transfection of HPV16 E6 gene enhances the resistance of human diploid fibroblasts to ionizing radiation. Oncogene 10: 2403-2408, 1995.
265. [264] Unger, C., Kress, S., Buchmann, A. and Schwarz, M. γ-Irradiation-induced micronuclei from mouse hepatoma cells accumulate high levels of the tumor suppressor protein p53. Cancer Res. 54: 3651-3655, 1994.
266. [265] van Laar, T., Steegenga, W., Jochemsen, A., Terleth, C. and van der Eb, A. Bloom's syndrome cells GM1492 lack detectable p53 protein but exhibit normal G1 cell-cycle arrest after UV irradiation. Oncogene 981-983, 1994.
267. [266] Vousden, K.H. Regulation of the cell cycle by viral oncoproteins. Semin. Cancer Biol. 6: 109-116, 1995.
268. [267] Wahl, A.F., Donaldson, K.L., Fairchild, G., Lee, F.Y.F., Foster, S.A., Demers, G.W. and Galloway, D.A. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat. Med. 2: 72-79, 1996.
269. [268] Wang, X.W., Yeh, H., Schaeffer, L., Roy, R., Moncollin, V., Egly, J.-M., Wang, Z., Friedberg, E.C., Evans, M.K., Taffe, B.C., Bohr, V.A., Weeda, G., Hoeijmakers, J.H.J., Forrester, K. and Harris, C.C. p53 modulation of TFIIH-associated nucleotide excision repair activity. Nat. Genet. 10: 188-195, 1995.
270. 1 cell cycle arrest and transactivation of WAF1 and bax. Cell Growth Differ. 6: 1071-1075, 1995.
271. [270] Wang, Y. and Prives, C. Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin-dependent kinases. Nature 376: 88-91, 1995.
272. [271] Warenius, H., Browning, P., Britten, R., Peacock, J. and Rapp, U. C-raf-1 proto-oncogene expression relates to radiosensitivity rather than radioresistance. Eur. J. Cancer 30: 369-375, 1994.
273. [272] West, C.M.L., Davidson, S.E., Burt, P.A. and Hunter, R.D. The intrinsic radiosensitivity of cervical carcinoma: correlations with clinical data. Int. J. Radiat. Oncol. Biol. Phys. 31: 841-846, 1995.
274. [273] Wheeler, J.A., Stephens, L.C., Tornos, C., Eifel, P.J., Ang, K.K., Milas, L., Allen, P.K. and Meyn, R.E. 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, 1995.
275. [274] White, E., Chiou, S.-K., Rao, L., Sabbatini, R. and Lin, H.-J. Control of p53-dependent apoptosis by E1B, Bcl-2, and Ha-ras proteins. Cold Spring Harbor Symposia on Quantitative Biology LIX: 395-402, 1994.
276. [275] Wilson, G.D., Richman, P.I., Dische, S., Saunders, M.I., Robinson, B., Daley, F.M. and Ross, D.A. p53 status of head and neck cancer: relation to biological characteristics and outcome of radiotherapy. Br. J. Cancer 71: 1248-1252, 1995.
277. [276] Winston, J.T., Coats, S.R., Wang, Y.-Z. and Pledger, J.J. Regulation of the cell cycle machinery by oncogenic ras. Oncogene 12: 127-134, 1996.
278. [277] Withers, H.R. and Taylor, J. Interfraction interval and dose-response in RTOG trials-regarding Fu et al. (Letter to Editor) Int. J. Radiat. Oncol. Biol. Phys. 32: 1266-1267, 1994.
279. [278] Wong, C.S., Van Dyke, J., Milosevic, M. and Laperriere, N. Radiation myelopathy following single courses of radiotherapy and retreatment. Int. J. Radiat. Oncol. Biol. Phys. 30: 575-581, 1994.
280. [279] Wu, X. and Levine, A.J. p53 and E2F-1 cooperate to mediate apoptosis. Proc. Natl. Acad. Sci. USA 91: 3602-3606, 1994.
281. WAF1 signalling pathway. Oncogene 12: 1077-1082, 1996.
282. [281] Xia, F., Wang, X., Wang, Y.-H., Tsang, N.-M., Yandell, D.W., Kelsey, K.T. and Liber, H.L. Altered p53 status correlates with differences in sensitivity to radiation-induced mutation and apoptosis in two closely related human lymphoblast lines. Cancer Res. 55: 12-15, 1995.
283. [282] Xiong, Y., Hannon, G., Zhong, H., Casso, D., Kobayashi, R. and Beach, D. p21 is a universal inhibitor of cyclin kinases. Nature 366: 701-704, 1993.
284. [283] Xu, C., Meikrantz, W., Schlegel, R. and Sager, R. The human papilloma virus 16E6 gene sensitizes human mammary epithelial cells to apoptosis induced by DNA damage. Proc. Natl. Acad. Sci. USA 92: 7829-7833, 1995.
285. [284] Yamaizumi, M. and Sugano, T. UV-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle. Oncogene 9: 2775-2784, 1994.
286. [285] Yang, C., Cirielly, C., Capogrossi, M.C. and Pasaniti, A. Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of prostatic tumor cells. Cancer Res. 55: 4210-4213, 1995.
287. [286] Yin, D.X. and Schimke, R.T. BCL-2 expression delays drug-induced apoptosis but does not increase clonogenic survival after drug treatment in HeLa cells. Cancer Res. 55: 4922-4928, 1995.
288. [287] Yin, Y., Tainsky, M., Bischoff, F.Z., Streng, L.C.D. and Wahl, G. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 70: 937-948, 1992.
289. [288] Zaffaroni, N., Benini, E., Gornati, D., Bearzatto, A. and Silverstrini, R. Lack of a correlation between p53 protein expression and radiation response in human tumor primary cultures. Stem Cells 13: 77-85, 1995.
290. [289] Zakian, V.A. ATM-related genes: what do they tell us about functions of the human gene? Cell 82: 685-687, 1995.
291. [290] Zambetti, G., Olson, D., Labow, M. and Levine, A.J. A mutant p53 protein is required for maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs. Proc. Natl. Acad. Sci. USA 89: 3952-3956, 1992.
292. [291] Zambetti, G. and Levine, A.J. A comparison of the biological activities of wild-type and mutant p53. FASEB J. 7: 855-865, 1993.
293. [292] Zhan, Q., Bae, I., Kastan, M.B. and Fornace, Jr. A.J. The p53-dependent γ-ray response of GADD45. Cancer Res. 54: 2755-2760, 1994.
294. [293] Zhan, Q., Fan, S., Bae, I., Guillouf, C., Liebermann, D.A., O'Connor, P.M. and Fornace, Jr. A.J. Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene 9: 3743-3751, 1994.
295. [294] Zhang, H., Hannon, G. and Beach, D. p21-containing cyclin kinases exist in both active and inactive states. Genes Dev. 8: 1750-1758, 1994.
296. [295] Zhang, W., Funk. W.D., Wright, W.E., Shay, J.W. and Deisseroth, A.B. Novel DNA binding of p53 mutants and their role in transcriptional activation. Oncogene 8: 2555-2559, 1993.
297. [296] Zhang, W.-W., Alemany, R., Wang, J., Koch, P.E., Ordonez, N.G. and Roth, J.A. Safety evaluation of Ad5CMV-p53 in vitro and in vivo. Hum. Gene Ther. 6: 155-164, 1995.
298. 1-block and p53 status in six human cell lines. Radiother. Oncol. 37: 20-28, 1995.