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Relationship Between the Antioxidant Enzyme DT-Diaphorase and Tumor Response to Mitomycin C Treatment

  • Chris A. Pritsos
  • Lani L. Pardini
  • Andrew J. Elliott
  • Ronald S. Pardini
Part of the Basic Life Sciences book series (BLSC, volume 49)

Abstract

The flavoprotein DT-diaphorase (NAD(P)H: quinone oxidoreductase, EC 1.6.99.2) is an enzyme which has been described as catalyzing the two-electron reduction of quinoid compounds to their representative hydro-quinone forms.1 The enzymatic reduction of quinones to their respective hydroquinones may represent part of the cellular defense mechanism against quinone-induced toxicity, because fully reduced quinones are capable of being conjugated by sulfate, sugars and amino acids and subsequently excreted.2 Both chemically and in biological systems, however, it is easier to reduce quinones by one electron to their semiquinones than by two electrons to their hydroquinone forms. The formation of these semiquinone radicals can lead to alkylation reactions and/or reactions with molecular oxygen to form oxygen radicals, resulting in oxidative stress and quinone toxicity. This mechanism of toxicity has been suggested to be responsible for at least part of the mechanism of antineoplastic activity for some of the quinoid anticancer drugs such as Adriamycin (Adr) and mitomycin C (MMC).3,4 Because DT-diaphorase reduces quinones by two electrons and thereby circumvents the potentially toxic one-electron reduction reactions of these compounds, it is possible that tumor response to treatment by these compounds may be greatly influenced by the endogeneous DT-diaphorase activity in the tumors.

Keywords

Tumor Weight Athymic Nude Mouse Quinone Oxidoreductase Untreated Tumor Semiquinone Radical 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Chris A. Pritsos
    • 1
  • Lani L. Pardini
    • 1
  • Andrew J. Elliott
    • 1
  • Ronald S. Pardini
    • 1
  1. 1.Department of BiochemistryUniversity of NevadaRenoUSA

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