Zur Rolle Von P53 Und Zum Einfluss Von Cadmiumchlorid Auf Dna-Reparaturprozesse Und Zellzykluskontrolle
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Zur Rolle Von P53 Und Zum Einfluss Von Cadmiumchlorid Auf Dna-Reparaturprozesse Und Zellzykluskontrolle

Zur Rolle Von P53 Und Zum Einfluss Von Cadmiumchlorid Auf Dna-Reparaturprozesse Und Zellzykluskontrolle


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About the Book

In der vorliegenden Arbeit wurde die Beteiligung des Tumorsuppressorproteins p53 an wichtigen zellularen Schutzmechanismen zur Aufrechterhaltung der genomischen Stabilitat untersucht. Dafur wurden zum einen menschliche Lungenkrebszellen der Linie A549 verwendet, von denen mittels RNA-Interferenz Klone mit stabil verminderter p53-Expression generiert wurden. Zum anderen wurde eine humane Kolonkarzinomzelllinie (HCT116) eingesetzt, von der auch eine isogene p53-defiziente Zelllinie zur Verfugung stand. Die Rolle von p53 in der DNA-Reparatur wurde nach Inkubation mit Benzo[a]pyrendiolepoxid (BPDE) sowie nach Bestrahlung mit UVC untersucht. Nach Inkubation mit BPDE waren Bildung und Reparatur der DNA-Addukte unabhangig vom p53-Status der untersuchten Zellen. Die Reparatur UVC-induzierter Cyclobutanpyrimidindimere (CPD) war demgegenuber bei den p53-defizienten HCT116 Zellen nach 24 h um etwa 25 % vermindert. Die zusatzliche Inkubation mit Cadmiumchlorid ergab weder in den HCT116 Zellen noch in den A549 Zellen eine Reparaturhemmung. Fur den unterschiedlichen Einfluss von p53 auf die Reparatur UVC- und BPDE-induzierter DNA-Schaden konnten einerseits Unterschiede in der Schadenserkennung verantwortlich sein. Zum anderen konnte die Anzahl der induzierten DNA-Schaden Einfluss auf die Abhangigkeit des Reparaturprozesses von p53 nehmen. Untersuchungen zur Rolle von p53 in der Zellzykluskontrolle wurden nach Behandlung der Zellen mit Actinomycin D durchgefuhrt. In den A549 und in den HCT116 Zellen konnte dabei eine Abhangigkeit der Zellzyklusregulation von p53 am G1/S- und am G2/M-Ubergang festgestellt werden. Die Effekte auf den Zellzyklus nach Inkubation mit Cadmium, BPDE oder nach UVC-Bestrahlung waren hingegen unabhangig vom p53-Status der untersuchten Zellen. Zusammenfassend lasst sich feststellen, dass die Rolle von p53 in der DNA-Reparatur in den untersuchten Zelllinien vielschichtig ist und sowohl vom DNA-Schadenstyp als auch vom Schadensausmass abhangig ist. Weitere Untersuchungen sind notwendig, um zu einem umfassenderen Verstandnis zu gelangen.


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Product Details
  • ISBN-13: 9783832517656
  • Publisher: Logos Verlag Berlin
  • Binding: Paperback
  • Language: German
  • Returnable: N
  • Spine Width: 0 mm
  • Width: 145 mm
  • ISBN-10: 3832517650
  • Publisher Date: 20 Dec 2007
  • Height: 210 mm
  • No of Pages: 150
  • Series Title: German
  • Weight: 110 gr


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Zur Rolle Von P53 Und Zum Einfluss Von Cadmiumchlorid Auf Dna-Reparaturprozesse Und Zellzykluskontrolle
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