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Some characteristics of two azoreductase systems in rat liver. Relevance to the activity of 2-[4'-di(2"-bromopropyl)-aminophenylazo]benzoic acid (CB10-252), a compound possessing latent cytotoxic activity.
Metadata
Journalchemico-biological interactions3.723Date
1975-Nov
Publication Type
Journal Article
Comparative Study
Volume
1975-Nov / 11 : 329-42
Author
Autrup H , Warwick GP
DoiPMIDMESH
Animals
Azo Compounds
Cecum
Cell Fractionation
Cytosol
Enzyme Induction
Flavin Mononucleotide
Flavin-Adenine Dinucleotide
Hydrogen-Ion Concentration
Kinetics
Liver
Male
Methylcholanthrene
Microsomes, Liver
NADH, NADPH Oxidoreductases
Organ Specificity
Oxidoreductases
Phenobarbital
Rats
Subcellular Fractions
Abstract
The system involved in the reduction of 2-[4'-di(2''-bromopropyl) aminophenylazolbenzoic acid (CB10-252), an agent designed for treating primary liver cell cancer, has been demonstrated to be localised mainly in the 108 000 X g supernatant fraction of rat liver homogenate. It is also present in other organs particularly in the spleen. DAB-azoreductase as shown previously is present almost entirely in the microsomal fraction and is found in high concentration only in liver. The pH maximum for CB10-252-azoreductase implying the importance of the 2'-carboxyl group in determining substrate specificity. The use of enzyme inhibitors and other additives showed that CB10-252 WAS NOT AXANTHINE OXIDASE OR DIHYDROFOLATE REDUCTASE. Its activity was not affected by carbon monoxide, phenobarbitone (PB), or 3-methylcholanthrene (MC) pretreatment. Enhancement of the activity by ferrous ions and FAD indicated that at least part of the reduction system could involve a flavoprotein with FAD as the prosthetic group. The activity of CB10-252-azoreductase and methylred-azoreductase was reduced by menadione (vitamin K3), cyanide and propylgallate. A diaphorase preparation from pig heart reduced both CB10-252 and methylred with both NADPH- and NADH-generating systems.
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3.7
Chem Biol Interactchemico-biological interactions
Metadata
LocationIreland
FromELSEVIER IRELAND LTD

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