• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
10.11606/T.42.2008.tde-22092008-170922
Document
Author
Full name
Luis Francisco Zirnberger Batista
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Menck, Carlos Frederico Martins (President)
Camargo, Anamaria Aranha
Durigon, Edison Luiz
Kowaltowski, Alicia Juliana
Reis, Luis Fernando Lima
Title in Portuguese
Mecanismos de indução de apoptose pela presença de danos ao DNA: um estudo sobre o papel de p53 na resistência de células de glioma a agentes quimioterápicos.
Keywords in Portuguese
Apoptose
Cultura de células
Danos do DNA
Mecanismos de controle celular
Neoplasias
Reparação do DNA
Abstract in Portuguese
A geração de lesões ao DNA possui diversos efeitos biológicos em células de mamíferos, como inibição da replicação do DNA, ativação de vias de reparo de DNA, mutagênese e indução de apoptose. Este último pode ter conseqüências deletérias para o organismo, mas também pode trazer benefícios, como impedir que uma célula com mutações seja perpetuada, possivelmente dando origem a um tumor. Há ainda muito por se descobrir sobre os mecanismos responsáveis pela indução de morte celular por apoptose após a geração de danos ao DNA. Neste trabalho iremos demonstrar que a replicação do DNA lesado é um evento necessário para indução de apoptose por luz UV, e que a inibição dessa replicação é capaz de evitar a morte celular mesmo em células deficientes em reparo de DNA. Será mostrado também que os agentes quimioterápicos Temozolomida, ACNU e BCNU são capazes de induzir apoptose em células de glioma, em um processo controlado por p53, que dependendo do agente utilizado determina a resposta a ser adotada pelas células, seja reparo de DNA ou indução de apoptose.
Title in English
Mechanisms of apoptosis induction by DNA damage: a study on the role of p53 to the resistance that glioma cells present to chemotherapeutical agents.
Keywords in English
Apoptosis
Cell culture
DNA damage
DNA repair
Mechanisms of cell control
Neoplasias
Abstract in English
Induction of DNA lesions leads to several different endpoints in mammalian cells, such as replication blockage, activation of DNA repair pathways, mutagenesis and induction of apoptosis. Although apoptosis induction might be involved in deleterious conditions, it can also bring benefit, as for instance to avoid the uncontrolled propagation of a mutated cell. The molecular mechanisms leading to apoptosis induction by DNA damage still remain largely under covered. This work provides evidence that the replication of damaged -DNA works as a trigger for UV-induced apoptosis. Surprisingly, even in DNA repair-deficient cells the inhibition of damaged-DNA replication is able to protect from apoptosis induction. This work also indicates that the chemotherapeutical agents Temozolomide, ACNU and BCNU are able to trigger apoptosis in human glioma cells, in a manner that is tightly controlled by the tumor suppressor gene p53, which depending upon the agent used will determine if the lesion will be removed by DNA repair or if cells will trigger apoptosis.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2008-09-24
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
Centro de Informática de São Carlos
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2021. All rights reserved.