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Expression of the Escherichia coli enzyme nitroreductase (NTR) in mammalian cells enables them to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), leading to interstrand DNA cross-linking and apoptosis in both proliferating and quiescent cells. In the work reported here, we used human hepatocellular carcinoma and squamous carcinoma cell lines constitutively expressing NTR to demonstrate that the ntr/CB1954 system results in potent, long-lasting antitumoral effects in mice. We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ.

Original publication

DOI

10.1038/sj.cgt.7700171

Type

Journal article

Journal

Cancer Gene Ther

Publication Date

05/2000

Volume

7

Pages

721 - 731

Keywords

Animals, Apoptosis, Aziridines, Carcinoma, Hepatocellular, Carcinoma, Squamous Cell, Cross-Linking Reagents, Dose-Response Relationship, Drug, Escherichia coli, Head and Neck Neoplasms, Humans, Immunohistochemistry, Liver Neoplasms, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Necrosis, Neoplasm Transplantation, Neoplasms, Experimental, Nitroreductases, Prodrugs, Remission Induction, Time Factors, Tumor Cells, Cultured