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Induction of NAD(P)H:quinone reductase in murine hepatoma cells by phenolic antioxidants, azo dyes, and other chemoprotectors: a model system for the study of anticarcinogens.

Abstract
Exposure of murine hepatoma (Hepa 1c1c7) cells to a variety of chemical agents known to protect animals against the neoplastic, mutagenic, and other toxic effects of chemical carcinogens results in dose- and time-dependent inductions of NAD(P)H:quinone reductase (EC 1.6.99.2). This enzyme protects against quinone toxicity by promoting obligatory two-electron reductions that divert quinones from oxidative cycling or direct interactions with critical nucleophiles. Quinone reductase levels are stable in culture, are easily measured, and are useful markers for the inductive effects of chemoprotective agents. The Hepa 1c1c7 system responds to chemoprotective compounds such as phenolic antioxidants (e.g., BHA [3(2)-tert-butyl-4-hydroxyanisole], BHT (3,5-ditert-butyl-4-hydroxytoluene), and tert-butylhydroquinone), lipophilic azo dyes belonging to the 1,1'-azonaphthalene, Sudan I (1-phenylazo-2-naphthol), and Sudan III [1-(4-phenylazophenylazo)-2-naphthol] families, polycyclic aromatic hydrocarbons, coumarin and various other lactones, flavonoids, and certain sulfur compounds (e.g., benzylisothiocyanate, dithiolthiones, and dithiocarbamates), all of which are recognized enzyme inducers and chemoprotectors in vivo. Quinone reductase induction in Hepa 1c1c7 cells therefore provides a simple, versatile, and reliable system for the evaluation of the potency, kinetics, and mechanism of action of anticarcinogens.
AuthorsM J De Long, H J Prochaska, P Talalay
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 83 Issue 3 Pg. 787-91 (Feb 1986) ISSN: 0027-8424 [Print] UNITED STATES
PMID3080750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antioxidants
  • Azo Compounds
  • Benzoquinones
  • Carcinogens
  • Coumarins
  • Lactones
  • Polycyclic Compounds
  • Quinones
  • benzoquinone
  • NAD(P)H Dehydrogenase (Quinone)
  • Quinone Reductases
Topics
  • Animals
  • Antioxidants (pharmacology)
  • Azo Compounds (pharmacology)
  • Benzoquinones
  • Carcinogens (antagonists & inhibitors)
  • Chemical Phenomena
  • Chemistry
  • Coumarins (pharmacology)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Induction
  • Kinetics
  • Lactones (pharmacology)
  • Liver Neoplasms, Experimental (enzymology)
  • Mice
  • NAD(P)H Dehydrogenase (Quinone)
  • Polycyclic Compounds (pharmacology)
  • Quinone Reductases (biosynthesis)
  • Quinones (pharmacology)
  • Structure-Activity Relationship

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