Format

Send to

Choose Destination
Free Radic Biol Med. 2000 Aug;29(3-4):231-40.

Persuasive evidence that quinone reductase type 1 (DT diaphorase) protects cells against the toxicity of electrophiles and reactive forms of oxygen.

Author information

1
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

An extensive body of evidence supports the conclusion that by catalyzing obligatory two-electron reductions of quinones to hydroquinones, NAD(P)H:quinone reductase (QR1) protects cells against the deleterious effects of redox cycling of quinones, their ability to deplete glutathione, and to produce neoplasia. The effects of elevation of QR1 levels by various enzyme inducers, inhibition of the enzyme by dicumarol, and genetic deletion of the enzyme (knockout mouse) are all consistent with the proposed protective functions. Measurement of QR1 activity in murine hepatoma cells grown in 96-well microtiter plates has provided a rapid and quantitative method for detecting inducer activity and determining inducer potency. This constitutes a strategy for the identification of potential chemoprotectors against cancer. Epidemiological studies show that humans who are genetically deficient in QR1 are more susceptible to the hematological toxicity and carcinogenicity of benzene exposure, and may be more susceptible to the development of a number of malignant tumors.

PMID:
11035251
DOI:
10.1016/s0891-5849(00)00300-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center