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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

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
; ;

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-di-tert-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.

Research Organization:
Johns Hopkins Univ. School of Medicine, Baltimore, MD
OSTI ID:
6216558
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 83:3; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIOXIDANTS
AROMATICS
AZO COMPOUNDS
AZO DYES
BIOCHEMISTRY
BODY
CHEMISTRY
COENZYMES
DIGESTIVE SYSTEM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DYES
ENZYME INDUCTION
ENZYMES
GENE REGULATION
GLANDS
HEPATOMAS
HYDROXY COMPOUNDS
LIVER
LIVER CELLS
MAMMALS
MICE
NADP
NEOPLASMS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHENOLS
QUINONES
RESPONSE MODIFYING FACTORS
RODENTS
SOMATIC CELLS
TIME DEPENDENCE
VERTEBRATES