Strahlenbiologische Charakterisierung des murinen Lewis-Lung-Modells

Hauptbestandteil der Arbeit war die strahlenbiologische Charakterisierung muriner LLC1-Zellen in vitro. Dabei handelt es sich um in Kultur überführte Einzelzellen eines bei in vivo Experimenten weit verbreiteten Tumormodells der Maus. Die soliden, entdifferenzierten Tumorzellverbände in vivo ents...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: Eberle, Fabian
Beteiligte: Engenhart-Cabillic (Prof.Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2013
Medizin
Ausgabe:http://dx.doi.org/10.17192/z2013.0138
Schlagworte:
Online Zugang:PDF-Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!

1. RAHN, J. J., ADAIR, G. M. & NAIRN, R. S. 2010. Multiple roles of ERCC1-XPF in mammalian interstrand crosslink repair. Environ Mol Mutagen, 51, 567-81.


2. TAKENAGA, K. 1986. Modification of the metastatic potential of tumor cells by drugs. Cancer Metastasis Rev, 5, 67-75.


3. POUGET, J. P. & MATHER, S. J. 2001. General aspects of the cellular response to low-and high-LET radiation. Eur J Nucl Med, 28, 541-61.


4. POMP, J., WIKE, J. L., OUWERKERK, I. J., HOOGSTRATEN, C., DAVELAAR, J., SCHRIER, P. I., LEER, J. W., THAMES, H. D. & BROCK, W. A. 1996. Cell density dependent plating efficiency affects outcome and interpretation of colony forming assays. Radiother Oncol, 40, 121-5.


5. STRASSER, A., HUANG, D. C. & VAUX, D. L. 1997. The role of the bcl-2/ced-9 gene family in cancer and general implications of defects in cell death control for tumourigenesis and resistance to chemotherapy. Biochim Biophys Acta, 1333, F151-78.


6. STOREY, B. T., PITTMAN, H. K., CHRISTIAN, J. F., HAISCH, C. E. & VERBANAC, K. M. 2004. Characterization of Lewis lung clonal variants in a model of syngeneic pulmonary murine metastases. Clin Exp Metastasis, 21, 265-73.


7. SONG, H., HOLLSTEIN, M. & XU, Y. 2007. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol, 9, 573-80.


8. VAN ATTIKUM, H. & GASSER, S. M. 2005. The histone code at DNA breaks: a guide to repair? Nat Rev Mol Cell Biol, 6, 757-65.


9. PRASHER, J. M., LALAI, A. S., HEIJMANS-ANTONISSEN, C., PLOEMACHER, R. E., HOEIJMAKERS, J. H., TOUW, I. P. & NIEDERNHOFER, L. J. 2005. Reduced hematopoietic reserves in DNA interstrand crosslink repair- deficient Ercc1-/-mice. EMBO J, 24, 861-71.


10. TAKAOKA, A., ADACHI, M., OKUDA, H., SATO, S., YAWATA, A., HINODA, Y., TAKAYAMA, S., REED, J. C. & IMAI, K. 1997. Anti-cell death activity promotes pulmonary metastasis of melanoma cells. Oncogene, 14, 2971-7.


11. ROGAKOU, E. P., NIEVES-NEIRA, W., BOON, C., POMMIER, Y. & BONNER, W. M. 2000. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem, 275, 9390-5.


12. OLAUSSEN, K. A., MOUNTZIOS, G. & SORIA, J. C. 2007. ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung cancer. Curr Opin Pulm Med, 13, 284-9.


13. WANG, Q., ZAMBETTI, G. P. & SUTTLE, D. P. 1997. Inhibition of DNA topoisomerase II alpha gene expression by the p53 tumor suppressor. Mol Cell Biol, 17, 389-97.


14. STEPHENS, L. C., ANG, K. K., SCHULTHEISS, T. E., MILAS, L. & MEYN, R. E. 1991. Apoptosis in irradiated murine tumors. Radiat Res, 127, 308-16.


15. PALAYOOR, S. T., MACKLIS, R. M., BUMP, E. A. & COLEMAN, C. N. 1995. Modulation of radiation-induced apoptosis and G2/M block in murine T-lymphoma cells. Radiat Res, 141, 235-43.


16. PEAK, M. J., WANG, L., HILL, C. K. & PEAK, J. G. 1991. Comparison of repair of DNA double-strand breaks caused by neutron or gamma radiation in cultured human cells. Int J Radiat Biol, 60, 891-8.


17. REED, E., DABHOLKAR, M., THORNTON, K., THOMPSON, C., YU, J. J. & BOSTICK-BRUTON, F. 2000. Evidence for in the appearance of mRNAs of nucleotide excision repair genes, in human ovarian cancer tissues. Oncol Rep, 7, 1123-8.


18. PUCK, T. T. & MARCUS, P. I. 1956. Action of x-rays on mammalian cells. J Exp Med, 103, 653-66.


19. SHTIVELMAN, E. 1997. A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma. Oncogene, 14, 2167-73.


20. OLTVAI, Z. N., MILLIMAN, C. L. & KORSMEYER, S. J. 1993. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 74, 609-19.


21. PFAFFL, M. W., TICHOPAD, A., PRGOMET, C. & NEUVIANS, T. P. 2004. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper--Excel-based tool using pair-wise correlations. Biotechnol Lett, 26, 509-15.


22. KCl, Carl Roth GmbH + Co. KG, Karlsruhe, Deutschland 11,36 g Na2HPO4, Merck KGaA, Darmstadt, Germany 2 g KH2PO4, Merck KGaA, Darmstadt, Germany dH20 (auf 1 l)


23. 12 well Platte, SARSTEDT AG & Co., Nümbrecht, Deutschland Deckgläser Otto E. Kobe KG, Marburg, Deutschland Falcon 15 ml, SARSTEDT AG & Co., Nümbrecht, Deutschland Falcon 50 ml, SARSTEDT AG & Co., Nümbrecht, Deutschland Kryoröhrchen Nunc, Thermo Fisher Scientific Inc, Waltham, USA Pasteurpipetten Otto E. Kobe KG, Marburg, Deutschland Petrischale 3, 5 cm Nunc, Thermo Fisher Scientific Inc, Waltham, USA Petrischale 3, 5 & 10 cm, SARSTEDT AG & Co., Nümbrecht, Deutschland Pipettenspitzen, Eppendorf AG, Hamburg, Deutschland Pipetten 1, 5, 10 & 25 ml, SARSTEDT AG & Co., Nümbrecht, Deutschland Zellkulturflasche T25 SARSTEDT AG & Co., Nümbrecht, Deutschland Zellkulturflasche T75 SARSTEDT AG & Co., Nümbrecht, Deutschland Medien und Zusätze für die Zellkultur Accutase, PAA Laboratories GmbH, Pasching, Austria Trypsin-EDTA, PAA Laboratories GmbH, Pasching, Austria FCS, PAA Laboratories GmbH, Pasching, Austria PBS, PAA Laboratories GmbH, Pasching, Austria DMSO (Dimethyl sulfoxide), Sigma-Aldrich Co., St. Louis, USA PBS (Selbsterzeugnis) (1 l): Anhang 133


24. VILLUENDAS, R., PIRIS, M. A., ORRADRE, J. L., MOLLEJO, M., RODRIGUEZ, R. & MORENTE, M. 1991. Different bcl-2 protein expression in high-grade B-cell lymphomas derived from lymph node or mucosa-associated lymphoid tissue. Am J Pathol, 139, 989-93.


25. ROGAKOU, E. P., PILCH, D. R., ORR, A. H., IVANOVA, V. S. & BONNER, W. M. 1998. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem, 273, 5858-68.


26. PIZZOFERRATO, E., LIU, Y., GAMBOTTO, A. 2004. Ectopic expression of interferon regulatory factor-1 promotes human breast cancer cell death and results in reduced expression of survivin. Cancer Research, vol. 64, pp. 8381–8388.


27. E-Mail: fabian_bernhard_eberle@hotmail.com Geburtsdatum: 06.09.1980


28. ROTHKAMM, K. & LÖBRICH, M. 2003. 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, 5057-62.


29. TAKENAGA, K., NAKAMURA, Y. & SAKIYAMA, S. 1997. Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells. Oncogene, 14, 331-7.


30. RAKOZY, C., GRIGNON, D. J., SARKAR, F. H., SAKR, W. A., LITTRUP, P. & FORMAN, J. 1998. Expression of bcl-2, p53, and p21 in benign and malignant prostatic tissue before and after radiation therapy. Mod Pathol, 11, 892-9.


31. TRACEY, L., PEREZ-ROSADO, A., ARTIGA, M.J., CAMACHO, F.I., RODRIGUEZ, A., MARTINEZ, N. 2005. Expression of the NF-κB targets BCL2 and BIRC5/Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively. The Journal of Pathology, 206, 123–134.


32. SKLADANOWSKI, A. & LARSEN, A. K. 1997. Expression of wild-type p53 increases etoposide cytotoxicity in M1 myeloid leukemia cells by facilitated G2 to M transition: implications for gene therapy. Cancer Res, 57, 818-23.


33. SOKOLOV, M. V., DICKEY, J. S., BONNER, W. M. & SEDELNIKOVA, O. A. 2007. gamma-H2AX in bystander cells: not just a radiation-triggered event, a cellular response to stress mediated by intercellular communication. Cell Cycle, 6, 2210-2.


34. OVEJERA, A., JOHNSON, R. K. & GOLDIN, A. 1975. Growth Characteristics and Chemotherapeutic Response of Intavenously Implanted Lewis Lung Carcinoma. Cancer Chemother Rep, vol 5, 111-125.


35. TAMM, I., WANG, Y., SAUSVILLE, E., SCUDIERO, D. A., VIGNA, N., OLTERSDORF, T. & REED, J. C. 1998. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res, 58, 5315-20.


36. TAKENAGA, K., NAKAMURA, Y., ENDO, H. & SAKIYAMA, S. 1994. Involvement of S100-related calcium-binding protein pEL98 (or mts1) in cell motility and tumor cell invasion. Jpn J Cancer Res, 85, 831-9.


37. Apoptose Kit 019K4006, Sigma-Aldrich Co., St. Louis, USA) PI staining buffer: 50 µg/ml RNase A, Sigma-Aldrich Co., St. Louis, USA


38. ROGAKOU, E. P., BOON, C., REDON, C. & BONNER, W. M. 1999. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol, 146, 905-16.


39. WARTERS, R. L., ADAMSON, P. J., POND, C. D. & LEACHMAN, S. A. 2005. Melanoma cells express elevated levels of phosphorylated histone H2AX foci. J Invest Dermatol, 124, 807-17.


40. VAN LAMSWEERDE, A. L., HENRY, N. & VAES, G. 1983. Metastatic heterogeneity of cells from Lewis lung carcinoma. Cancer Res, 43, 5314-20.


41. PENG, C. Y., GRAVES, P. R., THOMA, R. S., WU, Z., SHAW, A. S. & PIWNICA- WORMS, H. 1997. Mitotic and G2 checkpoint control: regulation of 14- 3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science, 277, 1501-5.


42. Seetharam, 2010, Oxaliplatin resistance induced by ERCC1 up-regulation is abrogated by siRNA-mediated gene silencing in human colorectal cancer cells. Cancer Res, 30, 2531-2538


43. SANDRI, M. I., ISAACS, R. J., ONGKEKO, W. M., HARRIS, A. L., HICKSON, I. D., BROGGINI, M. & VIKHANSKAYA, F. 1996. p53 regulates the minimal promoter of the human topoisomerase IIalpha gene. Nucleic Acids Res, 24, 4464-70.


44. SENGUPTA, S. & HARRIS, C. C. 2005. p53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol, 6, 44-55.


45. PEARSON, M., CARBONE, R., SEBASTIANI, C., CIOCE, M., FAGIOLI, M., SAITO, S., HIGASHIMOTO, Y., APPELLA, E., MINUCCI, S., PANDOLFI, P. P. & PELICCI, P. G. 2000. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature, 406, 207-10.


46. SCHWEINFURTH, Y. E. 2007. Prozessierung und Reparatur von komplexen DNA-Schäden mikroskopische Analyse und Quantifizierung des phosphorylierten Histons H2AX und des Tumorsuppressors p53 [Online].


47. TAYLOR, W. R. & STARK, G. R. 2001. Regulation of the G2/M transition by p53. Oncogene, 20, 1803-15.


48. TAKASU, M., TADA, Y., WANG, J. O., TAGAWA, M. & TAKENAGA, K. 1999. Resistance to apoptosis induced by microenvironmental stresses is correlated with metastatic potential in Lewis lung carcinoma. Clin Exp Metastasis, 17, 409-16.


49. Penicillin/Streptomycin, PAA Laboratories GmbH, Pasching, Austria Poly-D-Lysine, Sigma-Aldrich Co., Saint Louis, USA Poly-L-Lysine, Sigma-Aldrich Co., Saint Louis, USA RPMI 1640, PAA Laboratories GmbH, Pasching, Austria Trypsin-EDTA, PAA Laboratories GmbH, Pasching, Austria FACS-Analyse FACS Gerät BD LSRII, Becton Dickinson GmbH,Franklin Lakes, USA FACS DiVa Software, Becton Dickinson GmbH, Franklin Lakes, USA FlowJo, Version 7.5.3, Three Stars Inc., Ashland, USA Ethanol, Sigma-Aldrich Co., St. Louis, USA


50. TAMAOKI, T., NOMOTO, H., TAKAHASHI, I., KATO, Y., MORIMOTO, M. & TOMITA, F. 1986. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun, 135, 397-402.


51. SUGIURA, K. & STOCK, C. C. 1955. Studies in a tumor spectrum. III. The effect of phosphoramides on the growth of a variety of mouse and rat tumors. Cancer Res, 15, 38-51.


52. ROTHE, G. 2007. Technische und methodische Grundlagen der Durchflusszytometrie. Grundlagen, Methoden und klinische Anwendungen der Durchflusszytometrie pp27-70.


53. RONINSON, I. B. 2003. Tumor cell senescence in cancer treatment. Cancer Res, 63, 2705-15.


54. THORNBERRY, N. A. & LAZEBNIK, Y. 1998. Caspases: enemies within. Science, 281, 1312-6.


55. SCHROEDER, A., MUELLER, O., STOCKER, S., SALOWSKY, R., LEIBER, M., GASSMANN, M., LIGHTFOOT, S., MENZEL, W., GRANZOW, M. & RAGG, T. 2006. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol, 7, 3.


56. TANAKA, H., ARAKAWA, H., YAMAGUCHI, T., SHIRAISHI, K., FUKUDA, S., MATSUI, K., TAKEI, Y. & NAKAMURA, Y. 2000. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature, 404, 42-9.


57. VOGELSTEIN, B., LANE, D. & LEVINE, A. J. 2000. Surfing the p53 network. Nature, 408, 307-10.


58. PFAFFL, M. W., HORGAN, G. W. & DEMPFLE, L. 2002. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res, 30, e36.


59. PAULL, T. T., ROGAKOU, E. P., YAMAZAKI, V., KIRCHGESSNER, C. U., GELLERT, M. & BONNER, W. M. 2000. A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol, 10, 886-95.


60. TAUCHI, H. & SAWADA, S. 1994. Analysis of mitotic cell death caused by radiation in mouse leukaemia L5178Y cells: apoptosis is the ultimate form of cell death following mitotic failure. Int J Radiat Biol, 65, 449- 55.