Induction of NAD(P)H:quinone reductase in human peripheral blood lymphocytes.
The induction of quinone reductase [QR; NAD(P)H:(quinone acceptor) oxidoreductase; EC 1.6.99.2] in cultured cells and animal tissues of rodents has provided useful information on mechanisms of protection against carcinogens. We have developed a simple and efficient microtiter plate assay for the direct measurement of QR basal activity and inducibility in human peripheral blood lymphocytes (unstimulated, mitogen-stimulated and Epstein-Barr virus-transformed) grown in suspension culture. In these cells, QR was induced by monofunctional (electrophilic) inducers (i.e. 1,2-dithiole-3-thione, dimethyl fumarate, methyl vinyl sulfone) but not by bifunctional inducers (i.e. 1,1'-azonaphthalene, beta-naphthoflavone, 2,3,7,8-tetrachlorodibenzo-p-dioxin). QR is a major enzyme of xenobiotic metabolism that carries out obligatory two-electron reductions and thereby protects cells against the toxicity of quinones. It is induced in many tissues coordinately with other enzymes that protect against electrophiles. Since lymphocytes can be sampled easily and repetitively in man, this system may provide a simple short-term marker for assessing the capacity of tissues to detoxify electrophiles, such as quinones, and for measuring the response to inducers.
Gordon
G B
GB
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Prochaska
H J
HJ
Yang
L Y
LY
D000328:Adult; D000368:Aged; D002472:Cell Transformation, Viral / Q000502:physiology; D002478:Cells, Cultured; D000069462:Dimethyl Fumarate; D004790:Enzyme Induction; D005260:Female; D005650:Fumarates / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000097:blood; D013450:Sulfones / Q000494:pharmacology; D013871:Thiones / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D005650:Fumarates; D008934:Mitogens; D013450:Sulfones; D013871:Thiones; D013876:Thiophenes; C060916:methyl vinyl sulfone; D016660:NAD(P)H Dehydrogenase (Quinone); D000069462:Dimethyl Fumarate; C049325:1,2-dithiol-3-thione