Persuasive evidence that quinone reductase type 1 (DT diaphorase) protects cells against the toxicity of electrophiles and reactive forms of oxygen

• Published in: Free radical biology & medicine Vol. 29; no. 3; pp. 231 - 240
• Main Authors: Dinkova-Kostova, Albena T, Talalay, Paul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2000
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Antioxidant response element (ARE); Antioxidants - metabolism; Benzene - toxicity; Carcinogens - antagonists & inhibitors; Carcinogens - toxicity; Chemoprotection; Drug Evaluation, Preclinical; Enhancer Elements, Genetic - genetics; Enzyme Induction - drug effects; Free radicals; Genetic Predisposition to Disease; hepatoma; Humans; Hydroquinones; Isothiocyanates; NAD(P)H Dehydrogenase (Quinone) - genetics; NAD(P)H Dehydrogenase (Quinone) - metabolism; quinone reductase 1; Reactive Oxygen Species - metabolism; Redox cycling; Sulforaphane; Thiocyanates - pharmacology; Hydroquinones; Antioxidant response element (ARE); Chemoprotection; Redox cycling; Free radicals; Sulforaphane; BHA; Benzene toxicity; BHT
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(00)00300-2

An extensive body of evidence supports the conclusion that by catalyzing obligatory two-electron reductions of quinones to hydroquinones, NAD(P)H:quinone reductase (QR1) protects cells against the deleterious effects of redox cycling of quinones, their ability to deplete glutathione, and to produce neoplasia. The effects of elevation of QR1 levels by various enzyme inducers, inhibition of the enzyme by dicumarol, and genetic deletion of the enzyme (knockout mouse) are all consistent with the proposed protective functions. Measurement of QR1 activity in murine hepatoma cells grown in 96-well microtiter plates has provided a rapid and quantitative method for detecting inducer activity and determining inducer potency. This constitutes a strategy for the identification of potential chemoprotectors against cancer. Epidemiological studies show that humans who are genetically deficient in QR1 are more susceptible to the hematological toxicity and carcinogenicity of benzene exposure, and may be more susceptible to the development of a number of malignant tumors.