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Titolo:
Role of redox cycling and activation by DT-diaphorase in the cytotoxicity of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB-1954) and its analogs
Autore:
Miskiniene, V; Sergediene, E; Nemeikaite, A; Segura-Aguilar, J; Cenas, N;
Indirizzi:
Inst Biochem, LT-2600 Vilnius, Lithuania Inst Biochem Vilnius Lithuania LT-2600 ochem, LT-2600 Vilnius, Lithuania Inst Immunol, LT-2600 Vilnius, Lithuania Inst Immunol Vilnius Lithuania LT-2600 munol, LT-2600 Vilnius, Lithuania Univ Stockholm, Wallenberg Lab, Dept Biochem, Biochem Toxicol Unit, S-10691 Stockholm, Sweden Univ Stockholm Stockholm Sweden S-10691 Unit, S-10691 Stockholm, Sweden
Titolo Testata:
CANCER LETTERS
fascicolo: 2, volume: 146, anno: 1999,
pagine: 217 - 222
SICI:
0304-3835(19991115)146:2<217:RORCAA>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELECTRON REDUCTION; ESCHERICHIA-COLI; TOXICITY; RADICALS; QUINONE; RATES;
Keywords:
5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB-1954); DT-diaphorase; cytotoxicity; redox cycling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
15
Recensione:
Indirizzi per estratti:
Indirizzo: Cenas, N Inst Biochem, Mokslininku 12, LT-2600 Vilnius, Lithuania Inst Biochem Mokslininku 12 Vilnius Lithuania LT-2600 Lithuania
Citazione:
V. Miskiniene et al., "Role of redox cycling and activation by DT-diaphorase in the cytotoxicity of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB-1954) and its analogs", CANCER LETT, 146(2), 1999, pp. 217-222

Abstract

In tumor cell lines with high content of DT-diaphorase (EC 1.6.99.2), the cytotoxicity of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB-1954) and its derivatives is exerted through DT-diaphorase-catalyzed formation of crosslinking species. However, little is known about other possible mechanisms of CB-1954 action. We have examined the toxicity of CB-1954 and its derivatives to bovine leukemia virus-transformed lamb fibroblasts (line FLK), which possessed moderate DT-diaphorase activity, 260 units/mg protein. The action ofthese compounds was accompanied by lipid peroxidation, their toxicity was decreased by desferrioxamine and antioxidant N,N'-diphenyI-p-phenylene diamine (DPPD), but, in most cases, not by dicumarol, an inhibitor of DT-diaphorase. Using multiparameter regression analysis, we have found that the toxicity of CB-1954 derivatives as well as that of several non-alkylating nitroaromatics, increased upon the increase in their single-electron reduction potential (E-7(1)) and octanol/water partition coefficient (P), and almost did not depend on their reactivity towards DT-diaphorase. It seems that in cell lines with a moderate amount of DT-diaphorase, the toxicity of CB-1954 and its analogs is exerted through their redox cycling. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:03:43