RT Journal Article SR Electronic T1 Quinone-Stimulated Superoxide Formation by Subcellular Fractions, Isolated Hepatocytes, and Other Cells JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 387 OP 394 VO 20 IS 2 A1 GARTH POWIS A1 BRUCE A. SVINGEN A1 PEGGY APPEL YR 1981 UL http://molpharm.aspetjournals.org/content/20/2/387.abstract AB Quinones can undergo enzymatic one-electron reduction to the semiquinone radical which, in the presence of molecular oxygen, can transfer an electron and form the superoxide anion radical (O2[unknown]). Isolated hepatocytes do not liberate appreciable amounts of O2[unknown]. Simple quinones, such as 2,5-dimethyl-p-benzoquinone, stimulate the formation of O2[unknown] by hepatocytes up to 15 nmoles/min/106 cells. Hepatocyte O2[unknown] formation stimulated by a variety of simple quinones and more complex antitumor quinones is maximal at a quinone one-electron reduction potential (E71) of -70 mV and qualitatively similar to the pattern of O2[unknown] formation seen with mitochondrial NADH:ubiquinone oxidoreductase and microsomal NADH-cytochrome b5 reductase. O2[unknown] production by microsomal NADPH-cytochrome P-450 reductase is maximal at a quinone E71 of -200 mV. Phenobarbital induction, which increases NADPH-cytochrome P-450 reductase, has no effect on O2[unknown]formation by hepatocytes. It is concluded that NADPH-cytochrome P-450 reductase activity is not rate-limiting for quinone-stimulated O2[unknown] formation by hepatocytes. The sulfonated stilbenes, 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene and 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene have no marked effect on the formation of O2[unknown]by hepatocytes, suggesting that O2[unknown] is not transported through anion channels in the plasma membrane. Ethanol has no effect on hepatocyte O2[unknown] formation, which suggests that intracellular NADH is not rate-limiting. Treatment of hepatocytes with diethyldithiocarbamate, which inhibits cytosolic and mitochondrial superoxide dismutase, increases O2[unknown] formation by hepatocytes over 2-fold. Feeding rats a copper-deficient diet, which also decreases hepatic cytosolic and mitochondrial superoxide dismutase, has no effect on the quinone-dependent formation of O2[unknown] by hepatocytes.