Redox transformations of quinone antitumor drugs in liver microsomes
- 18 July 1988
- journal article
- Published by Wiley in FEBS Letters
- Vol. 234 (2) , 459-463
- https://doi.org/10.1016/0014-5793(88)80138-8
Abstract
The hydroxyl radical has been spin trapped in microsomal and purified NADPH-cytochrome P-450 reductase systems in the presence of adriamycin, daunomycin and mitomycin C. The presence of a lag period in quinone-stimulated spin-adduct formation is associated with oxygen removal upon its reduction to H2O2. The hydroxy radical generation has been stimulated by the Fe-EDTA complex and completely inhibited by catalase. The mechanism of redox transformations of anthracyclines in a microsomal system has been proposed The single electron reduced quinone-containing anticancer antibiotics play the following roles: (i) they reduce oxygen to H2O2 and (ii) they reduce the ferric ions necessary for H2O2 decomposition with hydroxyl radical formation.Keywords
This publication has 22 references indexed in Scilit:
- Generation of OH radical during enzymatic reduction of 9,10‐anthraquinone‐2‐sulphonate Can semiquinone decompose hydrogen peroxide?FEBS Letters, 1987
- Reactions of the semiquinone free radicals of anti‐tumour agents with oxygen and iron complexesFEBS Letters, 1985
- Further studies on the generation of reactive oxygen species from activated anthracyclines and the relationship to cytotoxic action and cardiotoxic effectsBiochemical Pharmacology, 1982
- Effects of dietary iron deficiency on iron-sulfur proteins and bioenergetic functions of skeletal muscle mitochondriaBiochimica et Biophysica Acta (BBA) - Bioenergetics, 1982
- Evidence for the production of hydroxyl radicals from the adriamycin semiquinone and H2O2FEBS Letters, 1981
- Production of formaldehyde during metabolism of dimethyl sulfoxide by hydroxyl radical-generating systemsBiochemistry, 1981
- Spin-trapping and direct electron spin resonance investigations of the redox metabolism of quinone anticancer drugsBiochimica et Biophysica Acta (BBA) - General Subjects, 1980
- Considerations in the spin trapping of superoxide and hydroxyl radical in aqueous systems using 5,5-dimethyl-1-pyrroline-1-oxideBiochemical and Biophysical Research Communications, 1978
- Adriamycin stimulated superoxide formation in submitochondrial particlesChemico-Biological Interactions, 1977
- Hydroxylation of Aliphatic Compounds by Liver Microsomes, I. The Distribution Pattern of Isomeric AlcoholsHoppe-Seyler´s Zeitschrift Für Physiologische Chemie, 1970