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PMID: 3080750 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 3 ·1986-02-00 ·Pages 787-91

De Long MJ, Prochaska HJ, Talalay P

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.

MeSH Terms
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
Chemicals
Antioxidants Azo Compounds Benzoquinones Carcinogens Coumarins Lactones Polycyclic Compounds Quinones quinone NAD(P)H Dehydrogenase (Quinone) Quinone Reductases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
De Long M J
Prochaska H J
Talalay P
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42 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.3.787
Published
1986-02-00
Pages
787-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC322950
Subset
IM
Grants
NIGMS NIH HHS · GM07309 · United States
External Links
PubMed source DOI: 10.1073/pnas.83.3.787 PMC Full Text View journal details
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