Hydroxyurea is a teratogen; treatment of dams during organogenesis causes various malformations. Administration of a free radical scavenger ameliorates the embryotoxicity of hydroxyurea, suggesting that oxidative stress mediates this toxicity. The goal of this thesis was to test the hypothesis that superoxide, a reactive oxygen species, is involved. Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide to hydrogen peroxide. To elucidate the role of superoxide in mediating hydroxyurea teratogenicity, dams that were wildtype or hemizygous for hSOD1 were treated on gestation day 9 with saline (control) or hydroxyurea (400 or 600 mg/kg). Fetal death rate and weight were affected similarly by hydroxyurea treatment in litters from wildtype and hemizygous dams. However, fetuses from hemizygote dams exposed to 600 mg/kg hydroxyurea had fewer specific external and skeletal malformations when compared to wildtype dams. These data suggest that superoxide dismutase 1 protects fetuses against specific consequences of oxidative insult during organogenesis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.116029 |
| Date | January 2008 |
| Creators | Larouche, Geneviève. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 003134094, proquestno: AAIMR66966, Theses scanned by UMI/ProQuest. |
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