Elevation of quinone reductase activity by anticarcinogenic antioxidants

Abstract

NAD(P)H:quinone reductase exhibitis broad specificity in the reduction of endogenous and exogenous quinones and quinone imines, such as those derived from polycyclic aromatic carcinogens, phenolic steroids, vitamin K, and numerous therapeutic drugs. This enzyme is found in several cell compartment and is widely distributed among tissues. In contrast to several other flavoprotein dehydrogenases, quinone reductase catalyzes obligatorily two electron reductions. Extensive studies by Huggins and by others have shown that the quinone reductase in liver and some other tissues of rats is inducible by various polycyclic hydrocarbons and aromatic amines, as well as by certain azo dyes. Huggins perceived that the relative effectiveness of such compounds in inducing quinone reductase correlated with their abilities to protect against toxicity and carcinogenesis. Certain antioxidants are also known to protect against the tumorigenic and toxic effects of carcinogens. Studies on the mechanisms underlying the protective effects of BHA, BHT, ethoxyquin, and disulfiram have revealed that these compounds alter the activity profiles of several enzymes which metabolize carcinogenic and toxic compounds. We have observed that quinone reductase specific activity is increased markedly in mouse liver and several extrahepatic tissues in response to dietary BHA, ethoxyquin, and disulfiram, whereas BHT has been shown by others to enhance this enzymatic activity in rat liver. These findings confirm and extend the correlation between the ability to elevate quinone reductase activity and to confer protection against carcinogenesis and toxicity. The broad specificity of quinone reductase, its apparent inability to catalyze one electron reductions of quinones, its widespread distribution, and its inducibility by a variety of structurally dissimilar protective compounds, suggest that quinone reductase may play a significant local protective role in varous regions of the cell.