Validation of Nitroreductase, a Prodrug-activating Enzyme, Mediated Cell Death in Embryonic Zebrafish (Danio rerio)
Abstract:Escherichia coli gene nfsB encodes a nitroreductase (NTR) enzyme that converts prodrugs like metronidazole (Met) and CB 1954 to cytotoxic metabolites. My coworkers and I have validated this prodrug-enzyme system in zebrafish (Danio rerio) by ubiquitously expressing NTR–EGFP fusion protein and exposing these embyos to CB 1954 and Met. These embryos showed extensive gross pathologic changes and death by 24 h of incubation in the prodrugs. They also exhibited widespread and marked apoptotic changes by 8 h of incubation in Met. Neither the prodrugs themselves nor the NTR–EGFP fusion protein were toxic to the developing zebrafish embryos. Thus the NTR–CB 1954 and NTR–Met systems can be used to ablate a wide variety of cells and tissues in zebrafish embryos.
Document Type: Miscellaneous
Publication date: 2007-06-01
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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