Dokument

Zusammenfassung:
Jeder Mensch ist in seinem Leben einer gewissen Strahlendosis ausgesetzt. Diagnostische Verfahren in der Medizin bilden mit einem Anteil von ungefähr 14 % den größten vom Menschen verursachten Anteil an ionisierender Strahlung weltweit. Ionisierende Strahlung kann über verschiedene Schäden an der DNA zur Entstehung von Leukämie und anderen Krebserkrankungen führen. DNA-Doppelstrangbrüche (DSB) zählen dabei zu den bedeutendsten Schäden, die die Karzinogenese initiieren können. Darüber hinaus benötigen viele bildgebende Verfahren die Verwendung jodhaltiger Kontrastmittel, deren Nieren- und zytotoxischen Effekte teilweise bereits bekannt sind. Allerdings gibt es kaum Studien darüber, ob die Verwendung jodhaltiger Kontrastmittel einen Einfluss auf die Entstehung und Reparatur von DNA-Schäden hat, die durch diagnostische Röntgenstrahlung verursacht wurden. Obwohl in letzter Zeit bereits Hitze-induzierte γ-H2AX-Foci beschrieben wurden, sind Studien über den Einfluss unterschiedlicher Temperaturen auf die Induktion und Reparatur von Strahlen induzierten DSB selten und widersprüchlich. Besonders wenige Forschungsergebnisse existieren über die Kombination von Bestrahlung und hypothermischen Temperaturen. Im Rahmen dieser Arbeit wurde zur Quantifizierung von DNA-Doppelstrangbrüchen die Darstellung der γ-H2AX-Foci durch Immunfluoreszenz gewählt. Die Versuche wurden bei Raumtemperatur, 4 °C und 37 °C, jeweils mit und ohne Kontrastmittel durchgeführt. Um Aussagen über die Korrelation von Strahlendosis und der Induktion von DSB treffen zu können wurden humane Lymphozyten pro Versuchsreihe in vitro mit 20 mGy,100 mGy, 200 mGy und 1000 mGy bestrahlt. Die Lymphozyten wurden sofort, 30 min,1 h, 2 h und 24 h nach Bestrahlung fixiert, um die Reparatur der DSB über die Zeit zu messen. Die Ergebnisse der Arbeit zeigen einen lineare Zusammenhang zwischen der Strahlendosis und der Formation der γ-H2AX-Foci. Es zeigte sich ein Rückgang der Foci bis 24 h nach Bestrahlung, wobei das Level der Negativkontrolle nicht erreicht werden konnte. Bei den Versuchen mit Applikation von jodiertem Kontrastmittel während der Bestrahlung zeigte sich, dass die Formation der DSB bei Anwesenheit von Kontrastmittel gesteigert wurde. Zusätzlich zeigten die Ergebnisse, dass die Reparationskapazität bei den Versuchen mit Kontrastmittel nicht eingeschränkt war. Bei den Versuchen mit unterschiedlichen Bestrahlungstemperaturen zeigten sich eingeschränkte Reparationskapazitäten bei den Versuchen mit 4 °C.

Bibliographie / References

1. Jovanovic, M. und W.S. Dynan, (2006). "Terminal DNA structure and ATP influence binding parameters of the DNA-dependent protein kinase at an early step prior to DNA synapsis." Nucleic Acids Res 34(4): 1112-20.
2. Sedelnikova, O.A., A. Nakamura, O. Kovalchuk, I. Koturbash, S.A. Mitchell, S.A. Marino, D.J. Brenner und W.M. Bonner, (2007). "DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models." Cancer Res 67(9): 4295-302.
3. Nagasawa, H. und J.B. Little, (1999). "Unexpected sensitivity to the induction of mutations by very low doses of alpha-particle radiation: evidence for a bystander effect." Radiat Res 152(5): 552-7.
4. "Low-dose hypersensitivity: current status and possible mechanisms." Int J Radiat Oncol Biol Phys 49(2): 379-89.
5. Altaf, M., N. Saksouk und J. Cote, (2007). "Histone modifications in response to DNA damage." Mutat Res 618(1-2): 81-90.
6. "Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139." J Biol Chem 275(13): 9390-5.
7. Obe, G., C. Johannes und D. Schulte-Frohlinde, (1992). "DNA double-strand breaks induced by sparsely ionizing radiation and endonucleases as critical lesions for cell death, chromosomal aberrations, mutations and oncogenic transformation." Mutagenesis 7(1): 3-12.
8. Kinner, A., W. Wu, C. Staudt und G. Iliakis, (2008a). "Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin." Nucleic Acids Res 36(17): 5678-94.
9. Martin, C.J., (2008). "Radiation dosimetry for diagnostic medical exposures." Radiat Prot Dosimetry 128(4): 389-412.
10. Tremethick, D.J., (2007). "Higher-order structures of chromatin: the elusive 30 nm fiber." Cell 128(4): 651-4.
11. Ward, J.F., C.L. Limoli, P.M. Calabro-Jones und J. Aguilera, (1991). "An examination of the repair saturation hypothesis for describing shouldered survival curves." Radiat Res 127(1): 90-6.
12. Shiloh, Y., (2003). "ATM and related protein kinases: safeguarding genome integrity." Nat Rev Cancer 3(3): 155-68.
13. Röntgen, W.C., (1895) " Über eine neue Art von Strahlen (Vorläufige Mitteilung). " Sitzungsbericht der Physikalisch-medizinischen Gesellschaft zu Würzburg 9: 132-141.
14. Roti Roti, J.L., (2008). "Cellular responses to hyperthermia (40-46 degrees C): cell killing and molecular events." Int J Hyperthermia 24(1): 3-15.
15. Pilch, D.R., O.A. Sedelnikova, C. Redon, A. Celeste, A. Nussenzweig und W.M. Bonner, (2003). "Characteristics of gamma-H2AX foci at DNA double-strand breaks sites." Biochem Cell Biol 81(3): 123-9.
16. Prakash, L., (1981). "Characterization of postreplication repair in Saccharomyces cerevisiae and effects of rad6, rad18, rev3 and rad52 mutations." Mol Gen Genet 184(3): 471-8.
17. Kornberg, R.D., (1974). "Chromatin structure: a repeating unit of histones and DNA." Science 184(139): 868-71.
18. van Gent, D.C., J.H. Hoeijmakers und R. Kanaar, (2001). "Chromosomal stability and the DNA double-stranded break connection." Nat Rev Genet 2(3): 196-206.
19. Rydberg, B., (1996). "Clusters of DNA damage induced by ionizing radiation: formation of short DNA fragments. II. Experimental detection." Radiat Res 145(2): 200-9.
20. Ulrich, H.D., (2007). "Conservation of DNA damage tolerance pathways from yeast to humans." Biochem Soc Trans 35(Pt 5): 1334-7.
21. Solomon, R., (2007). "Contrast-induced nephropathy: update with special emphasis on patients with diabetes." Curr Diab Rep 7(6): 454-8.
22. Thomsen, H.S. und S.K. Morcos, (2003). "Contrast media and the kidney: European Society of Urogenital Radiology (ESUR) guidelines." Br J Radiol 76(908): 513-8.
23. Kampinga, H.H., Y.S. Hiemstra, A.W. Konings und E. Dikomey, (1997). "Correlation between slowly repairable double-strand breaks and thermal radiosensitization in the human HeLa S3 cell line." Int J Radiat Biol 72(3): 293-301.
24. Brehwens, K., E. Staaf, S. Haghdoost, A.J. Gonzalez und A. Wojcik, (2010). "Cytogenetic damage in cells exposed to ionizing radiation under conditions of a changing dose rate." Radiat Res 173(3): 283-9.
25. Norman, A., F.H. Adams und R.F. Riley, (1978). "Cytogenetic effects of contrast media and triiodobenzoic acid derivatives in human lymphocytes." Radiology 129(1): 199-203.
26. Reiser M., FP. Kuhn, J. Debus (2004). Radiologie. MLP Duale Reihe, Thieme Rich, T., R.L. Allen und A.H. Wyllie, (2000). "Defying death after DNA damage." Nature 407(6805): 777-83.
27. Takahashi, A., N. Yamakawa, E. Mori, K. Ohnishi, S. Yokota, N. Sugo, Y. Aratani, H. Koyama und T. Ohnishi, (2008). "Development of thermotolerance requires interaction between polymerase-beta and heat shock proteins." Cancer Sci 99(5): 973-8.
28. Wu, W., C. Zhang, Z. Chen, G. Zhang und J. Yang, (2009). "Differences in heating methods may account for variation in reported effects on gammaH2AX focus formation." Mutat Res 676(1-2): 48-53.
29. Sonoda, E., H. Hochegger, A. Saberi, Y. Taniguchi und S. Takeda, (2006). "Differential usage of non-homologous end-joining and homologous recombination in double strand break repair." DNA Repair (Amst) 5(9-10): 1021-9.
30. Wang, Z., (2001). "DNA damage-induced mutagenesis : a novel target for cancer prevention." Mol Interv 1(5): 269-81.
31. Ward, J.F., (1988). "DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability." Prog Nucleic Acid Res Mol Biol 3595-125.
32. Karran, P., (2000). "DNA double strand break repair in mammalian cells." Curr Opin Genet Dev 10(2): 144-50.
33. Kampinga, H.H. und A. Laszlo, (2005). "DNA double strand breaks do not play a role in heat-induced cell killing." Cancer Res 65(22): 10632-3; author reply 10633.
34. Rogakou, E.P., D.R. Pilch, A.H. Orr, V.S. Ivanova und W.M. Bonner, (1998). "DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139." J Biol Chem 273(10): 5858-68.
35. Niewolik, D., U. Pannicke, H. Lu, Y. Ma, L.V. Wang, P. Kulesza, E. Zandi, M.R. Lieber und K. Schwarz, (2006). "DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5' or 3' overhangs." J Biol Chem 281(45): 33900-9.
36. Shivji, M.K.K. und A.R. Venkitaraman, (2004). "DNA recombination, chromosomal stability and carcinogenesis: insights into the role of BRCA2." DNA Repair (Amst) 3(8-9): 835-43.
37. Takahashi, A. und T. Ohnishi, (2005). "Does gammaH2AX foci formation depend on the Presence of DNA double strand breaks?" Cancer Lett 229(2): 171-9.
38. Adams, F.H., A. Norman, R.S. Mello und D. Bass, (1977). "Effect of radiation and contrast media on chromosomes. Preliminary report." Radiology 124(3): 823-6.
39. Matsubara, S., S. Suzuki, H. Suzuki, Y. Kuwabara und T. Okano, (1982). "Effects of contrast medium on radiation-induced chromosome aberrations." Radiology 144(2): 295-301.
40. Rothkamm, K. und M. Lobrich, (2003a). "Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses." Proc Natl Acad Sci U S A 100(9): 5057-62.
41. Takahashi, A., H. Matsumoto, K. Nagayama, M. Kitano, S. Hirose, H. Tanaka, E. Mori, N. Yamakawa, J. Yasumoto, K. Yuki, K. Ohnishi und T. Ohnishi, (2004). "Evidence for the involvement of double-strand breaks in heat-induced cell killing." Cancer Res 64(24): 8839-45.
42. Riley, P.A., (1994). "Free radicals in biology: oxidative stress and the effects of ionizing radiation." Int J Radiat Biol 65(1): 27-33.
43. Stucki, M. und S.P. Jackson, (2006). "gammaH2AX and MDC1: anchoring the DNA- damage-response machinery to broken chromosomes." DNA Repair (Amst) 5(5): 534-43.
44. Ohnishi, K. und T. Ohnishi, (2001). "Heat-induced p53-dependent signal transduction and its role in hyperthermic cancer therapy." Int J Hyperthermia 17(5): 415-27.
45. Kaneko, H., K. Igarashi, K. Kataoka und M. Miura, (2005). "Heat shock induces phosphorylation of histone H2AX in mammalian cells." Biochem Biophys Res Commun 328(4): 1101-6.
46. West, M.H. und W.M. Bonner, (1980). "Histone 2A, a heteromorphous family of eight protein species." Biochemistry 19(14): 3238-45.
47. "Histone H2A variants H2AX and H2AZ." Curr Opin Genet Dev 12(2): 162-9.
48. Bassing, C.H., H. Suh, D.O. Ferguson, K.F. Chua, J. Manis, M. Eckersdorff, M. Gleason, R. Bronson, C. Lee und F.W. Alt, (2003). "Histone H2AX: a dosage-dependent suppressor of oncogenic translocations and tumors." Cell 114(3): 359-70.
49. Ward, I.M. und J. Chen, (2001). "Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress." J Biol Chem 276(51): 47759-62.
50. Peterson, C.L. und M. Laniel, (2004). "Histones and histone modifications." Curr Biol 14(14): R546-51.
51. Pages, V. und R.P.P. Fuchs, (2002). "How DNA lesions are turned into mutations within cells?" Oncogene 21(58): 8957-66.
52. Pirker, E., (1996). "Hundert Jahre Rontgenstrahlen. Der Beitrag osterreichischer Wissenschaftler zu ihrer Entdeckung und Nutzung." Wien Klin Wochenschr 108(1): 1-4.
53. Nevaldine, B., J.A. Longo und P.J. Hahn, (1994). "Hyperthermia inhibits the repair of DNA double-strand breaks induced by ionizing radiation as determined by pulsed-field gel electrophoresis." Int J Hyperthermia 10(3): 381-8.
54. Bowden, G.T. und M.D. Kasunic, (1981). "Hyperthermic potentiation of the effects of a clinically significant X-ray dose on cell survival, DNA damage, and DNA repair." Radiat Res 87(1): 109-20.
55. Nagasawa, H. und J.B. Little, (1992). "Induction of sister chromatid exchanges by extremely low doses of alpha-particles." Cancer Res 52(22): 6394-6.
56. BELLI, J.A. und F.J. BONTE, (1963). "Influence of temperature on the radiation response of mammalian cells in tissue culture." Radiat Res 18272-6.
57. Mould, R.F., (1995). "Invited review: Rontgen and the discovery of X-rays." Br J Radiol 68(815): 1145-76.
58. Singh, J. und A. Daftary, (2008). "Iodinated contrast media and their adverse reactions." J Nucl Med Technol 36(2): 69-74; quiz 76-7.
59. Joubert, A., M. Biston, C. Boudou, J. Ravanat, T. Brochard, A. Charvet, F. Esteve, J. Balosso und N. Foray, (2005). "Irradiation in presence of iodinated contrast agent results in radiosensitization of endothelial cells: consequences for computed tomography therapy." Int J Radiat Oncol Biol Phys 62(5): 1486-96.
60. Kraft, G., M. Kramer und M. Scholz, (1992). "LET, track structure and models. A review." Radiat Environ Biophys 31(3): 161-80.
61. Rothkamm, K., S. Balroop, J. Shekhdar, P. Fernie und V. Goh, (2007). "Leukocyte DNA damage after multi-detector row CT: a quantitative biomarker of low-level radiation exposure." Radiology 242(1): 244-51.
62. Sung, P. und H. Klein, (2006). "Mechanism of homologous recombination: mediators and helicases take on regulatory functions." Nat Rev Mol Cell Biol 7(10): 739-50.
63. Rogakou, E.P., C. Boon, C. Redon und W.M. Bonner, (1999). "Megabase chromatin domains involved in DNA double-strand breaks in vivo." J Cell Biol 146(5): 905-16.
64. Norman, A., S.T. Cochran und J.W. Sayre, (2001). "Meta-analysis of increases in micronuclei in peripheral blood lymphocytes after angiography or excretory urography." Radiat Res 155(5): 740-3.
65. Stojic, L., R. Brun und J. Jiricny, (2004). "Mismatch repair and DNA damage signalling." DNA Repair (Amst) 3(8-9): 1091-101.
66. Whitaker, S.J., S.N. Powell und T.J. McMillan, (1991). "Molecular assays of radiation- induced DNA damage." Eur J Cancer 27(7): 922-8.
67. West, S.C., (2003). "Molecular views of recombination proteins and their control." Nat Rev Mol Cell Biol 4(6): 435-45.
68. Vamvakas, S., E.H. Vock und W.K. Lutz, (1997). "On the role of DNA double-strand breaks in toxicity and carcinogenesis." Crit Rev Toxicol 27(2): 155-74.
69. Bonner, W.M., (2004). "Phenomena leading to cell survival values which deviate from linear-quadratic models." Mutat Res 568(1): 33-9.
70. "Quantitative detection of (125)IdU-induced DNA double-strand breaks with gamma-H2AX antibody." Radiat Res 158(4): 486-92.
71. Sung, P., L. Krejci, S. Van Komen und M.G. Sehorn, (2003). "Rad51 recombinase and recombination mediators." J Biol Chem 278(44): 42729-32.
72. Nickoloff, E.L. und P.O. Alderson, (2001). "Radiation exposures to patients from CT: reality, public perception, and policy." AJR Am J Roentgenol 177(2): 285-7.
73. Teoule, R., (1987). "Radiation-induced DNA damage and its repair." Int J Radiat Biol Relat Stud Phys Chem Med 51(4): 573-89.
74. Widel, M., S. Jedrus, B. Lukaszczyk, K. Raczek-Zwierzycka und A. Swierniak, (2003). " Radiation-induced micronucleus frequency in peripheral blood lymphocytes is correlated with normal tissue damage in patients with cervical carcinoma undergoing radiotherapy." Radiat Res 159(6): 713-21.
75. Kauffmann, G.W., E. Moser, R. Sauter (2006). Radiologie. Urban &Fischer, 3. Auflage Khanna, K.K. und S.P. Jackson, (2001). "DNA double-strand breaks: signaling, repair and the cancer connection." Nat Genet 27(3): 247-54.
76. Breen, A.P. und J.A. Murphy, (1995). "Reactions of oxyl radicals with DNA." Free Radic Biol Med 18(6): 1033-77.
77. Thompson, L.H. und D. Schild, (2002). "Recombinational DNA repair and human disease." Mutat Res 509(1-2): 49-78.
78. McGlynn, P. und R.G. Lloyd, (2002). "Recombinational repair and restart of damaged replication forks." Nat Rev Mol Cell Biol 3(11): 859-70.
79. Krogh, B.O. und L.S. Symington, (2004). "Recombination proteins in yeast." Annu Rev Genet 38233-71.
80. Mountford, P.J. und D.H. Temperton, (1992). "Recommendations of the International Commission on Radiological Protection (ICRP) 1990." Eur J Nucl Med 19(2): 77-9.
81. Redpath, J.L. und R.J. Antoniono, (1995). "Reduced temperature (22 degrees C) results in enhancement of cell killing and neoplastic transformation in noncycling HeLa x skin fibroblast human hybrid cells irradiated with low-dose-rate gamma radiation." Radiat Res 144(1): 102-6.
82. Valerie, K. und L.F. Povirk, (2003). "Regulation and mechanisms of mammalian double- strand break repair." Oncogene 22(37): 5792-812.
83. Shrivastav, M., L.P. De Haro und J.A. Nickoloff, (2008). "Regulation of DNA double- strand break repair pathway choice." Cell Res 18(1): 134-47.
84. Winans, L.F., W.C. Dewey und C.M. Dettor, (1972). "Repair of sublethal and potentially lethal x-ray damage in synchronous Chinese hamster cells." Radiat Res 52(2): 333-51.
85. Toprak, O., (2007). "Risk markers for contrast-induced nephropathy." Am J Med Sci 334(4): 283-90.
86. Berrington de Gonzalez, A. und S. Darby, (2004). "Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries." Lancet 363(9406): 345-51.
87. Tripodi, D., S. Lyons und D. Davies, (1971). "Separation of peripheral leukocytes by Ficoll density gradient centrifugation." Transplantation 11(5): 487-8.
88. Roti Roti, J.L., R.K. Pandita, J.D. Mueller, P. Novak, E.G. Moros und A. Laszlo, (2010). "Severe, short-duration (0-3 min) heat shocks (50-52 degrees C) inhibit the repair of DNA damage." Int J Hyperthermia 26(1): 67-78.
89. WEISS, L., (1960). "Some effects of hypothermia and hypoxia on the sensitivity of HeLa cells to x-rays." Int J Radiat Biol 220-7.
90. UNSCEAR. " Sources and Effects of Ionizing Radiation: Report to the General Assembly, with Scientific Annexes (United Nations Scientific Committee on the Effects of Atomic Radiation, New York). " Band 792000, 314.
91. Prise, K.M., O.V. Belyakov, M. Folkard und B.D. Michael, (1998). "Studies of bystander effects in human fibroblasts using a charged particle microbeam." Int J Radiat Biol 74(6): 793-8.
92. Vilenchik, M.M., (1989). "Studies of DNA damage and repair of thermal-and radiation- induced lesions in human cells." Int J Radiat Biol 56(5): 685-9.
93. Studium der Medizin an der Philipps-Universität Marburg, vorklinischer Teil 08/05 Physikum 08/05 -06/10
94. Shao, C., M. Folkard, B.D. Michael und K.M. Prise, (2004). "Targeted cytoplasmic irradiation induces bystander responses." Proc Natl Acad Sci U S A 101(37): 13495-500.
95. Tertial Abteilung für Chirurgie, 1. Teil: Charles S. Curtis Memorial Hospital, Neufundland (Kanada)
96. Virsik-Peuckert, R.P. und D. Harder, (1986). "Temperature and the formation of radiation-induced chromosome aberrations. II. The temperature dependence of lesion repair and lesion interaction." Int J Radiat Biol Relat Stud Phys Chem Med 49(4): 673-81.
97. Mould, R.F., (1998). "The discovery of radium in 1898 by Maria Sklodowska-Curie (1867-1934) and Pierre Curie (1859-1906) with commentary on their life and times." Br J Radiol 71(852): 1229-54.
98. Meek, K., S. Gupta, D.A. Ramsden und S.P. Lees-Miller, (2004). "The DNA-dependent protein kinase: the director at the end." Immunol Rev 200132-41.
99. Kim, S.H., J.H. Kim und E.W. Hahn, (1976). "The enhanced killing of irradiated HeLa cells in synchronous culture by hyperthermia." Radiat Res 66(2): 337-45.
100. Takahashi, A., E. Mori und T. Ohnishi, (2010). "The foci of DNA double strand break- recognition proteins localize with gammaH2AX after heat treatment." J Radiat Res (Tokyo) 51(1): 91-5.
101. Bajerska, A. und J. Liniecki, (1969). "The influence of temperature at irradiation in vitro on the yield of chromosomal aberrations in peripheral blood lymphocytes." Int J Radiat Biol Relat Stud Phys Chem Med 16(5): 483-93.
102. Raaphorst, G.P., C.E. Ng und D.P. Yang, (1999). "Thermal radiosensitization and repair inhibition in human melanoma cells: a comparison of survival and DNA double strand breaks." Int J Hyperthermia 15(1): 17-27.
103. Richmond, T.J. und C.A. Davey, (2003). "The structure of DNA in the nucleosome core." Nature 423(6936): 145-50.
104. Ward, J.F., (1990). "The yield of DNA double-strand breaks produced intracellularly by ionizing radiation: a review." Int J Radiat Biol 57(6): 1141-50.
105. Breimer, L.H. und T. Lindahl, (1985). "Thymine lesions produced by ionizing radiation in double-stranded DNA." Biochemistry 24(15): 4018-22.
106. Prakash, S. und L. Prakash, (2002). "Translesion DNA synthesis in eukaryotes: a one- or two-polymerase affair." Genes Dev 16(15): 1872-83.
107. Shcherbakova, P.V. und I.J. Fijalkowska, (2006). "Translesion synthesis DNA polymerases and control of genome stability." Front Biosci 112496-517.
108. Seibert, J.A. und J.M. Boone, (2005). "X-ray imaging physics for nuclear medicine technologists. Part 2: X-ray interactions and image formation." J Nucl Med Technol 33(1): 3-18.
109. Stiff, T., M. O'Driscoll, N. Rief, K. Iwabuchi, M. Lobrich und P.A. Jeggo, (2004). "ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation." Cancer Res 64(7): 2390-6.
110. "DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing." Clin Cancer Res 14(20): 6546-55.
111. Bassing, C.H., K.F. Chua, J. Sekiguchi, H. Suh, S.R. Whitlow, J.C. Fleming, B.C. Monroe, D.N. Ciccone, C. Yan, K. Vlasakova, D.M. Livingston, D.O. Ferguson, R. Scully und F.W. Alt, (2002). "Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX." Proc Natl Acad Sci U S A 99(12): 8173-8.
112. Symington, L.S., (2002). "Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair." Microbiol Mol Biol Rev 66(4): 630-70, table of contents.
113. "Induction of a bystander mutagenic effect of alpha particles in mammalian cells." Proc Natl Acad Sci U S A 97(5): 2099-104.
114. Rothkamm, K., I. Kruger, L.H. Thompson und M. Lobrich, (2003b). "Pathways of DNA double-strand break repair during the mammalian cell cycle." gvMol Cell Biol 23(16): 5706-15.
115. Bogliolo, M., A. Lyakhovich, E. Callen, M. Castella, E. Cappelli, M.J. Ramirez, A. Creus, R. Marcos, R. Kalb, K. Neveling, D. Schindler und J. Surralles, (2007). "Histone H2AX and Fanconi anemia FANCD2 function in the same pathway to maintain chromosome stability." EMBO J 26(5): 1340-51.
116. Uematsu, N., E. Weterings, K. Yano, K. Morotomi-Yano, B. Jakob, G. Taucher-Scholz, P. Mari, D.C. van Gent, B.P.C. Chen und D.J. Chen, (2007). "Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks." J Cell Biol 177(2): 219-29.
117. Michel, B., M.J. Flores, E. Viguera, G. Grompone, M. Seigneur und V. Bidnenko, (2001). "Rescue of arrested replication forks by homologous recombination." Proc Natl Acad Sci U S A 98(15): 8181-8.
118. Paques, F. und J.E. Haber, (1999). "Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae." Microbiol Mol Biol Rev 63(2): 349-404.
119. Paull, T.T., E.P. Rogakou, V. Yamazaki, C.U. Kirchgessner, M. Gellert und W.M. Bonner, (2000). "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage." Curr Biol 10(15): 886-95.

Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten