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Understanding the basis of 5-Bromo-2'-deoxuridine teratogen specificity in organogenesis stage mouse embryos

5-Bromo-2'-deoxyuridine (BrdU), a thymidine analogue, is genotoxic and teratogenic. The exposure of mouse embryos to BrdU at doses that cause malformations induces oxidative stress and an embryonic stress response characterized by an increase in c-Fos dependent AP-1 DNA binding. The goal of this thesis was to test the hypothesis that development is disturbed at sites where BrdU is incorporated into DNA, triggering oxidative stress and c-Fos induction. Gestation day 9 CD-1 mice were treated with BrdU and embryos were obtained for immunolocalization of BrdU, 8-oxoguanine, a biomarker for oxidative stress, and c-Fos. BrdU incorporation into DNA was dispersed throughout the embryo. In contrast, the staining for 8-oxoguanine and c-Fos were highest in the neuroepithelium. BrdU incorporation was not affected by the pre-administration of N-acetyl-cysteine (NAC), an anti-oxidant, although both 8-oxoguanine and c-Fos staining were decreased. Thus, the response of the embryo to insult is tissue specific.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.112624
Date January 2008
CreatorsGnanabakthan, Naveen.
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Pharmacology & Therapeutics.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 002731732, proquestno: AAIMR51270, Theses scanned by UMI/ProQuest.

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