Abstract
The gene encoding E. coli nitroreductase (NTR) was expressed in the luminal cells of the mammary gland of transgenic mice using the ovine beta-lactoglobulin promoter. Treatment of NTR expressing animals with the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) resulted in a rapid and selective killing of this population of cells whereas the closely associated myoepithelial cells were unaffected. NTR-mediated inducible cell ablation offers a number of advantages over the use of HSV1-tk for the selective killing of cells in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Aziridines / pharmacology*
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Cell Culture Techniques
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Female
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Gene Expression
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Genetic Therapy / methods*
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Immunoenzyme Techniques
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Lactation
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Lactoglobulins / genetics
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Mammary Glands, Animal / cytology
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Mammary Glands, Animal / drug effects
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Mice
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Mice, Transgenic
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Nitroreductases / genetics*
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Nitroreductases / metabolism
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Prodrugs / pharmacology*
Substances
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Antineoplastic Agents
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Aziridines
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Lactoglobulins
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Prodrugs
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tretazicar
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Nitroreductases