IMR Press / FBL / Volume 5 / Issue 3 / DOI: 10.2741/gutier

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

The metabolism of quinone-containing alkylating agents: free radical production and measurement
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1 The University of Maryland Greenebaum Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA
Front. Biosci. (Landmark Ed) 2000, 5(3), 629–638;
Published: 1 July 2000

The metabolism of quinone-containing antitumor agents involves enzymatic reduction of the quinone by one or two electrons. This reduction results in the formation of the semiquinone or the hydroquinone of the anticancer drug. The consequence of these enzymatic reductions is that the semiquinone yields its extra electron to oxygen with the formation of superoxide radical anion and the original quinone. This reduction by a reductase followed by oxidation by molecular oxygen (dioxygen) is known as redox-cycling and continues until the system becomes anaerobic. In the case of a two electron reduction, the hydroquinone could become stable, and as such, excreted by the organism in a detoxification pathway. In some cases such as aziridine quinones, the hydroquinone can be oxidized by one electron at a time resulting in the production of superoxide, the semiquinone and the parental quinone. Quinone anticancer agents upon reduction can also set up an equilibrium between the hydroquinone, the parental quinone and the semiquinone which results in a long-lived semiquinone. Depending on the compound, aziridine quinones, for example, this equilibrium is long lasting thus allowing for the detection of the semiquinone under aerobic conditions. This phenomenon is known as comproportionation-disporportionation equilibrium. The series of reviews in this Special Issue address the consequences of bioreduction of quinone alkylators used in the treatment of cancer. In this particular review we are interested in describing the phenomenon of redox-cycling, how it is measured, and the biological consequences of the presence of the semiquinone and the oxygen radicals generated.

Anticancer Agents
Redox Cycling
Oxygen Radicals
Quinone Alkylators
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