The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis

The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR) enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytot...

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Autores principales: FELMER,RICARDO N, CLARK,JOHN A
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2004
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000300009
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spelling oai:scielo:S0716-976020040003000092005-03-14The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosisFELMER,RICARDO NCLARK,JOHN A genetic ablation NTR/CB1954 adipocytes differentiation The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR) enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1) transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or lossinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.37 n.3 20042004-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000300009en10.4067/S0716-97602004000300009
institution Scielo Chile
collection Scielo Chile
language English
topic genetic ablation
NTR/CB1954
adipocytes
differentiation
spellingShingle genetic ablation
NTR/CB1954
adipocytes
differentiation
FELMER,RICARDO N
CLARK,JOHN A
The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
description The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR) enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1) transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss
author FELMER,RICARDO N
CLARK,JOHN A
author_facet FELMER,RICARDO N
CLARK,JOHN A
author_sort FELMER,RICARDO N
title The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
title_short The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
title_full The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
title_fullStr The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
title_full_unstemmed The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis
title_sort gene suicide system ntr/cb1954 causes ablation of differentiated 3t3l1 adipocytes by apoptosis
publisher Sociedad de Biología de Chile
publishDate 2004
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000300009
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