Induction of epidermal NAD(P)H:quinone reductase by chemical carcinogens: a possible mechanism for the detoxification |
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| Authors: | W A Khan M Das S Stick S Javed D R Bickers H Mukhtar |
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| Affiliation: | 1. Department of Dermatology, Case Western Reserve University, 10701 East Boulevard, Cleveland, Ohio 44106 USA;2. Department of Dermatology, Veterans Administration Medical Center, 10701 East Boulevard, Cleveland, Ohio 44106 USA;1. Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria;2. KMT Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria;3. Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Innsbruck, Austria;4. Institute of Molecular Biosciences, University of Graz, Graz, Austria;1. Institute of Molecular Health Sciences, Department of Biology, ETH Zürich, Zürich, Switzerland;2. Functional Genomics Center Zurich, University of Zurich/ETH Zürich, Zürich, Switzerland;3. Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;4. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland;5. Research Division of Biology and Pathobiology of the Skin, Department of Dermatology, Medical University of Vienna, Vienna, Austria;6. Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark;1. Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck, Austria;2. Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria;3. Department of Dermatology, University of California San Francisco, San Francisco, California;4. Center of Electron Microscopy Applied to Biology, Faculty of Medicine Rangueil, Toulouse III, Paul Sabatier University, Toulouse, France;5. Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria |
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| Abstract: | NAD(P)H:quinone reductase, which plays an important role in the detoxification of carcinogenic metabolites as well as oxidative cellular damage, was found to be present in epidermal cytosol where its specific activity far exceeds (140-160%) the corresponding hepatic value. The effect of topical application of crude coal tar, 3-methylcholanthrene and polychlorinated biphenyl Aroclor 1254, on epidermal and hepatic cytosolic NAD(P)H:quinone reductase activities was investigated in neonatal rats, Sencar and athymic nude mice. A single topical application of each agent resulted in significant increases in epidermal (185%-389%) and hepatic (150-255%) enzyme activities. This inducible enzyme may play an important role in the detoxification of reactive quinone species during the course of malignant neoplasia and against oxidative cellular damage in skin. |
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