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One- and Two-Electron-Mediated Reduction of Quinones: Enzymology and Toxicological Implications

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References

  • Amaya, Y., Yamazaki, K., Sato, M., Noda, K., Nishino, T., and Nishino, T. 1990. Proteolytic conversion of xanthine dehydrogenase from the NAD-dependent type to the O2-dependent type. Amino acid sequence of rat liver xanthine dehydrogenase and identification of the cleavage sites of the enzyme protein during irreversible conversion by trypsin. J. Biol. Chem. 265:14170–14175.

    PubMed  CAS  Google Scholar 

  • Arscott, L. D., Gromer, S., Schirmer, R. H., Becker, K and Williams, C. H. Jr. 1997. The mechanism of thioredoxin reductase from human placenta is similar to the mechanisms of lipoamide dehydrogenase and glutathione reductase and is distinct from the mechanism of thioredoxin reductase from Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 94:3621–3626.

    PubMed  CAS  Google Scholar 

  • Atalla, A., Breyer-Pfaff, U., and Maser, E. 2000. Purification and characterization of oxidoreductases catalyzing carbonyl reduction of the tobacco-specific nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in human liver cytosol. Xenobiotica 30:755–769.

    PubMed  CAS  Google Scholar 

  • Bachur, N. R., Gordon, S. L., Gee, M. V., and Kon, H. 1979. NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals. Proc. Natl. Acad. Sci. U.S.A. 76:954–957.

    PubMed  CAS  Google Scholar 

  • Backes, W. L., and Reker-Backes, C. E. 1988. The effect of NADPH concentration on the reduction of cytochrome P-450 LM2. J. Biol. Chem. 263:247–253.

    PubMed  CAS  Google Scholar 

  • Battelli, M. G., Lorenzoni, E., and Stripe, F. 1973. Milk xanthine oxidase type D (dehydrogenase) and type O (oxidase). Purification, interconversion and some properties. Biochem. J. 131:191–198.

    PubMed  CAS  Google Scholar 

  • Bauer, A. K., Faiola, B., Abernethy, D. J., Marchan, R., Pluta, L. J., Wong, V. A., Roberts, K., Jaiswal, A. K., Gonzalez, F. J., Butterworth, B. E, Borghoff, S., Parkinson, H., Everitt, J., and Recio, L. 2003. Genetic susceptibility to benzene-induced toxicity: role of NADPH: quinone oxidoreductase-1. Cancer Res. 63:929–935.

    PubMed  CAS  Google Scholar 

  • Beall, H. D., Liu, Y., Siegel, D., Bolton, E. M., Gibson, N. W., and Ross, D. 1996. Role of NAD(P)H:quinone oxidoreductase (DT-diaphorase) in cytotoxicity and induction of DNA damage by streptonigrin. Biochem. Pharmacol. 51:645–652.

    PubMed  CAS  Google Scholar 

  • Beall, H. D., Winski, S., Swann, E., Hudnott, A. R., Cotterill, A. S., O'Sullivan, N., Green, S. J., Bien, R., Siegel, D., Ross, D., and Moody, C. J. 1998. Indolequinone antitumor agents: correlation between quinone structure, rate of metabolism by recombinant human NAD(P)H:quinone oxidoreductase, and in vitro cytotoxicity. J. Med. Chem. 41:4755–4766.

    PubMed  CAS  Google Scholar 

  • Beall, H. D., Mulcahy, R. T., Siegel, D., Traver, R. D., Gibson, N. W., and Ross, D. 1994. Metabolism of bioreductive antitumor compounds by purified rat and human DT-diaphorases. Cancer Res. 54:3196–3201.

    PubMed  CAS  Google Scholar 

  • BeBoer, C., and Dietz, A. 1976. The description and antibiotic production of Streptomyces hygroscopicus var. Geldanus. J. Antibiot. (Tokyo) 29:1182–1188.

    CAS  Google Scholar 

  • Begleiter A., Leith, M. K., Patel, D., and Hasinoff, B. B. 2007. Role of NADPH cytochrome P450 reductase in activation of RH1. Cancer Chemother. Pharmacol. 60:713–723.

    Google Scholar 

  • Behrsing, H. P., Amin, K., Ip, C., Jimenez, L., and Tyson, C. A. 2005. In vitro detection of differential and cell-specific hepatobiliary toxicity induced by geldanamycin and 17-allylaminogeldanamycin in rats. Toxicol. In Vitro 19:1079–1088.

    PubMed  CAS  Google Scholar 

  • Belcourt, M. F., Hodnick, W. F., Rockwell, S., and Sartorelli, A. C. 1996. Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450) reductase. Proc. Natl. Acad. Sci. U.S.A. 93:456–460.

    PubMed  CAS  Google Scholar 

  • Benchekroun, N. M., Myers, C. E., and Sinha, B. K. 1994. Free radical formation by ansamycin benzoquinone in human breast tumor cells: implications for cytotoxicity and resistance. Free Rad. Biol. Med. 17:191–200.

    PubMed  CAS  Google Scholar 

  • Boorstein, R. J., and Pardee, A. B. 1984. Beta-lapachone greatly enhances MMS lethality to human fibroblasts. Biochem. Biophys. Res. Commun. 118:828–834.

    PubMed  CAS  Google Scholar 

  • Boothman, D. A., and Pardee, A. B. 1989. Inhibition of radiation-induced neoplastic transformation by beta-lapachone. Proc. Natl. Acad. Sci. U.S.A. 86:4963–4967.

    PubMed  CAS  Google Scholar 

  • Boveris, A., Docampo, R., Turrens, J. F., and Stoppani, A. O. 1978. Effect of beta-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi. Biochem. J. 175:431–439.

    PubMed  CAS  Google Scholar 

  • Brown, J. M., Terada, L. S., Grosso, M. A., Whitmann, G. J., Velasco, S. E., Patt, A., Harken, A. H., and Repine, J. E. 1988. Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts. J. Clin. Invest. 81:1297–1301.

    PubMed  CAS  Google Scholar 

  • Brunmark, A., Cadenas, E., Segura-Aguilar, J., Lind, C., and Ernster, L. 1988. DT-diaphorase-catalyzed two-electron reduction of various p-benzoquinone- and 1,4-naphthoquinone epoxides. Free Rad. Biol. Med. 5:133–143.

    PubMed  CAS  Google Scholar 

  • Buffinton, G. D., Ollinger, K., Brunmark, A., and Cadenas, E. 1989. DT-diaphorase-catalysed reduction of 1,4-naphthoquinone derivatives and glutathionyl-quinone conjugates. Effect of substituents on autoxidation rates. Biochem. J. 257:561–571.

    PubMed  CAS  Google Scholar 

  • Buryanovskyy, L., Fu, Y., Boyd, M., Ma, Y., Hsieh, T. C., Wu, J. M., and Zhang, Z. 2004. Crystal structure of quinone reductase 2 in complex with resveratrol. Biochemistry 43:11417–11426.

    PubMed  CAS  Google Scholar 

  • Butler, J. 1998. Redox cycling antitumor drugs. In DNA and Free Radicals. Techniques, Mechanisms and Applications, eds. B. Halliwell, and O. I. Aruoma, pp. 131–154. London: OICA International.

    Google Scholar 

  • Butler, J., and Hoey, B. M. 1993. The one-electron reduction potential of several substrates can be related to their reduction rates by cytochrome P-450 reductase. Biochim. Biophys. Acta 1161:73–78.

    PubMed  CAS  Google Scholar 

  • Cecchini, G. 2003. Function and structure of complex II of the respiratory chain. Annu. Rev. Biochem. 72:77–109.

    PubMed  CAS  Google Scholar 

  • Celli, C. M., Tran, N., Knox, R., and Jaiswal, A. K. 2006. NRH:quinone oxidoreductase 2 (NQO2) catalyzes metabolic activation of quinines and anti-tumor drugs. Biochem. Pharmacol. 72:366–376.

    PubMed  CAS  Google Scholar 

  • Cenas, N., Nemeikaite-Ceniene, A., Sergediene, E., Nivinskas, H., Anusevicius, Z., and Sarlauskas, J. 2001. Quantitative structure–activity relationships in enzymatic single-electron reduction of nitroaromatic explosives: implications for their cytotoxicity. Biochim Biophys Acta 1528:31–38.

    PubMed  CAS  Google Scholar 

  • Chau, Y. P., Shiah, S. G., Don, M. J., and Kuo, M. L. 1998. Involvement of hydrogen peroxide in topoisomerase inhibitor beta-lapachone-induced apoptosis and differentiation in human leukemia cells. Free Rad. Biol. Med. 24:660–670.

    PubMed  CAS  Google Scholar 

  • Chen, S., Hwang, J., and Deng, P. S. 1993. Inhibition of NAD(P)H:quinone acceptor oxidoreductase by flavones: a structure–activity study. Arch. Biochem. Biophys. 302:72–77.

    PubMed  CAS  Google Scholar 

  • Cresteil, T., and Jaiswal, A. K. 1991. High levels of expression of the NAD(P)H:quinone oxidoreductase (NQO1) gene in tumor cells compared to normal cells of the same origin. Biochem. Pharmacol. 42:1021–1027.

    PubMed  CAS  Google Scholar 

  • Cullen, J. J., Hinkhouse, M. M., Grady, M., Gaut, A. W., Liu, J., Zhang, Y. P., Weydert, C. J., Domann, F. E., and Oberley, L. W. 2003. Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. Cancer Res. 63:5513–5520.

    PubMed  CAS  Google Scholar 

  • Curt, G. A., Kelley, J. A., Kufta, C. V., Smith, B. H., Kornblith, P. L., Young, R. C., and Collins, J. M. 1983. Phase II and pharmacokinetic study of aziridinylbenzoquinone [2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone, diaziquone, NSC182986] in high-grade gliomas. Cancer Res. 43:6102–6105.

    PubMed  CAS  Google Scholar 

  • Danson, S., Ranson, M., Denneny, O., Cummings, J., and Ward, T. H. 2007. Validation of the comet-X assay as a pharmacodynamic assay for measuring DNA cross-linking produced by the novel anticancer agent RH1 during a phase I clinical trial. Cancer Chemother. Pharmacol. 60:851–861.

    Google Scholar 

  • De Haan, L. H., Boerboom, A. M., Rietjens, I. M., van Capelle, D., De Ruijter, A. J., Jaiswal, A. K., and Aarts, J. M. 2002. A physiological threshold for protection against menadione toxicity by human NAD(P)H:quinone oxidoreductase (NQO1) in Chinese hamster ovary (CHO) cells. Biochem. Pharmacol. 64:1597–1603.

    PubMed  Google Scholar 

  • De Long, M. J., Prochaska, H. J., and Talalay, P. 1986. 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. Proc. Natl. Acad. Sci. U.S.A. 83:787–791.

    PubMed  Google Scholar 

  • Dehn, D. L., Inayat-Hussain, S. H., and Ross, D. 2005. RH1 induces cellular damage in an NAD(P)H:quinone oxidoreductase 1-dependent manner: relationship between DNA cross-linking, cell cycle perturbations, and apoptosis. J. Pharmacol. Exp. Ther. 313:771–779.

    PubMed  CAS  Google Scholar 

  • Dehn, D. L., Siegel, D., Swann, E., Moody, C. J., and Ross, D. 2003. Biochemical, cytotoxic, and genotoxic effects of ES936, a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1, in cellular systems. Mol. Pharmacol. 64:714–720.

    PubMed  CAS  Google Scholar 

  • Dehn, D. L., Winski, S. L., and Ross, D. 2004. Development of a new isogenic cell-xenograft system for evaluation of NAD(P)H:quinone oxidoreductase-directed antitumor quinones: evaluation of the activity of RH1. Clin. Cancer Res. 10:3147–3155.

    PubMed  CAS  Google Scholar 

  • Della Corte, E., Gozzetti, G., Novello, F., and Stirpe, F. 1969. Properties of the xanthine oxidase from human liver. Biochim. Biophys. Acta 191:164–166.

    PubMed  CAS  Google Scholar 

  • Denny, W. A. 2005. Hypoxia-activated anticancer drugs. Expert Opin. Ther. Pat. 15:635–646.

    CAS  Google Scholar 

  • Dikalov, S., Landmesser, U., and Harrison, D. G. 2002. Geldanamycin leads to superoxide formation by enzymatic and non-enzymatic redox cycling. Implications for studies of Hsp90 and endothelial cell nitric-oxide synthase. J. Biol. Chem. 277:25480–25485.

    PubMed  CAS  Google Scholar 

  • Dirix, L. Y., Tonnesen, F., Cassidy, J., Epelbaum, R., ten Bokkel Huinink, W. W., Pavlidis, N., Sorio, R., Gamucci, T., Wolff, I., Te Velde, A., Lan, J., and Verweij, J. 1996. EO9 phase II study in advanced breast, gastric, pancreatic and colorectal carcinoma by the EORTC Early Clinical Studies Group. Eur. J. Cancer 32:2019–2022.

    Google Scholar 

  • Everett, S. A., Naylor, M. A., Nolan, J., Patel, K. B., and Wardman, P. 1998. Indolequinone bioreductive drugs: kinetic factors which influence selectivity for hypoxia. Anticancer Drug Des. 13:635–653.

    PubMed  CAS  Google Scholar 

  • Fleming, R. A., Drees, J., Loggie, B. W., Russell, G. B., Geisinger, K. R., Morris, R. T., Sachs, D., and McQuellon, R. P. 2002. Clinical significance of a NAD(P)H: quinone oxidoreductase 1 polymorphism in patients with disseminated peritoneal cancer receiving intraperitoneal hyperthermic chemotherapy with mitomycin C. Pharmacogenetics 12:31–37.

    PubMed  CAS  Google Scholar 

  • Frei, B., Kim, M. C., and Ames, B. N. 1990. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc. Natl. Acad. Sci. U.S.A. 87:4879–4883.

    PubMed  CAS  Google Scholar 

  • Friedlos, F., Jarman, M., Davies, L. C., Boland, M. P., and Knox, R. J. 1992. Identification of novel reduced pyridinium derivatives as synthetic co-factors for the enzyme DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2). Biochem. Pharmacol. 44:25–31.

    PubMed  CAS  Google Scholar 

  • Gan, Y., Mo, Y., Kalns, J. E., Lu, J., Danenberg, K., Danenberg, P., Wientjes, M. G., and Au, J. L. 2001. Expression of DT-diaphorase and cytochrome P450 reductase correlates with mitomycin C activity in human bladder tumors. Clin. Cancer Res. 7:1313–1319.

    PubMed  CAS  Google Scholar 

  • Gibson, N. W., Hartley, J. A., Butler, J., Siegel, D., and Ross, D. 1992. Relationship between DT-diaphorase-mediated metabolism of a series of aziridinylbenzoquinones and DNA damage and cytotoxicity. Mol. Pharmacol. 42:531–536.

    PubMed  CAS  Google Scholar 

  • Goetz, M. P., Toft, D. O., Ames, M. M., and Erlichman, C. 2003. The Hsp90 chaperone complex as a novel target for cancer therapy. Ann. Oncol. 14:1169–1176.

    PubMed  CAS  Google Scholar 

  • Graves, P. R., Kwiek, J. J., Fadden, P., Ray, R., Hardeman, K., Coley, A. M., Foley, M., and Haystead, T. A. 2002. Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol. Pharmacol. 62:1364–1372.

    PubMed  CAS  Google Scholar 

  • Gregor, W., Staniek, K., Nohl, H., and Gille, L. 2006. Distribution of tocopheryl quinone in mitochondrial membranes and interference with ubiquinone-mediated electron transfer. Biochem. Pharmacol. 71:1589–1601.

    PubMed  CAS  Google Scholar 

  • Grenert, J. P., Sullivan, W. P., Fadden, P., Haystead, T. A., Clark, J., Mimnaugh, E., Krutzsch, H., Ochel, H. J., Schulte, T. W., Sausville, E., Neckers, L. M., and Toft, D. O. 1997. The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J. Biol. Chem. 272:23843–23850.

    PubMed  CAS  Google Scholar 

  • Grivennikova, V. G., and Vinogradov, A. D. 2006. Generation of superoxide by the mitochondrial Complex I. Biochim. Biophys. Acta 1757:553–561.

    PubMed  CAS  Google Scholar 

  • Guo, W., Reigan, P., Siegel, D., Zirrolli, J., Gustafson, D., and Ross, D. 2005. Formation of 17-allylamino-demethoxygeldanamycin (17-AAG) hydroquinone by NAD(P)H:quinone oxidoreductase 1: role of 17-AAG hydroquinone in heat shock protein 90 inhibition. Cancer Res. 65:10006–10015.

    PubMed  CAS  Google Scholar 

  • Guo, W., Reigan, P., Siegel, D., Zirrolli, J., Gustafson, D., and Ross, D. 2006. The bioreduction of a series of benzoquinone ansamycins by NAD(P)H:quinone oxidoreductase 1 to more potent heat shock protein 90 inhibitors, the hydroquinone ansamycins. Mol. Pharmacol. 70:1194–1203.

    PubMed  CAS  Google Scholar 

  • Gustafson, D. L., and Pritsos, C. A. 1992. Bioactivation of mitomycin C by xanthine dehydrogenase from EMT6 mouse mammary carcinoma tumors. J. Natl. Cancer Inst. 84:1180–1185.

    PubMed  CAS  Google Scholar 

  • Gutierrez, P. L. 2000. The metabolism of quinone-containing alkylating agents: free radical production and measurement. Front. Biosci. 5:629–638.

    Google Scholar 

  • Halliwell, B., and Gutteridge, J. M. 1985. The importance of free radicals and catalytic metal ions in human diseases. Mol. Aspects Med. 8:89–193.

    PubMed  CAS  Google Scholar 

  • Halliwell, B., and Gutteridge, J. M. 1999. Radical chemistry: thermodynamics and kinetics. In Free Radicals in Biology and Medicine, pp. 39–48. Oxford: Oxford University Press.

    Google Scholar 

  • Hargreaves, R. H., O'Hare, C. C., Hartley, J. A., Ross, D., Butler, J. 1999. Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents. J. Med. Chem. 42:2245–2250.

    PubMed  CAS  Google Scholar 

  • Harris, C. M., Sanders, S. A., and Massey, V. 1999. Role of the flavin midpoint potential and NAD binding in determining NAD versus oxygen reactivity of xanthine oxidoreductase. J. Biol. Chem. 274:4561–4569.

    PubMed  CAS  Google Scholar 

  • Hille, R. 1996. The mononuclear molybdenum enzymes. Chem. Rev. 96: 2757–2816.

    PubMed  CAS  Google Scholar 

  • Hille, R., and Massey, V. 1981. Studies on the oxidative half-reaction of xanthine oxidase. J. Biol. Chem. 256: 9090–9095.

    PubMed  CAS  Google Scholar 

  • Hille, R., and Nishino, T. 1995. Flavoprotein structure and mechanism. Xanthine oxidase and xanthine dehydrogenase. FASEB J. 9:995–1003.

    PubMed  CAS  Google Scholar 

  • Hodnick, W. F., and Sartorelli, A. C. 1993. Reductive activation of mitomycin C by NADH:cytochrome b 5 reductase. Cancer Res. 53:4907–4912.

    PubMed  CAS  Google Scholar 

  • Hollander, P. M., and Ernster, L. 1975. Studies on the reaction mechanism of DT diaphorase. Action of dead-end inhibitors and effects of phospholipids. Arch. Biochem. Biophys. 169:560–567.

    PubMed  CAS  Google Scholar 

  • Hsieh, T. C., Wang, Z., Hamby, C. V., and Wu, J. M. 2005. Inhibition of melanoma cell proliferation by resveratrol is correlated with upregulation of quinone reductase 2 and p53. Biochem. Biophys. Res. Commun. 334:223–230.

    PubMed  CAS  Google Scholar 

  • Hultquist, D. E., and Passon, P. G. 1971. Catalysis of methaemoglobin reduction by erythrocyte cytochrome b 5 and cytochrome b 5 reductase. Nat. New Biol. 229:252–254.

    PubMed  CAS  Google Scholar 

  • Iskander, K., and Jaiswal, A. K. 2005. Quinone oxidoreductases in protection against myelogenous hyperplasia and benzene toxicity. Chem. Biol. Interact. 30:153–154.

    Google Scholar 

  • Iyanagi, T. 1977. Redox properties of microsomal reduced nicotinamide adenine dinucleotide-cytochrome b 5 reductase and cytochrome b 5. Biochemistry 16:2725–2730.

    PubMed  CAS  Google Scholar 

  • Iyanagi, T. 2005. Structure and function of NADPH-cytochrome P450 reductase and nitric oxide synthase reductase domain. Biochem. Biophys. Res. Commun. 338:520–528.

    PubMed  CAS  Google Scholar 

  • Iyanagi, T., Makino, N., and Mason, H. S. 1974. Redox properties of the reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 and reduced nicotinamide adenine dinucleotide-cytochrome b 5 reductases. Biochemistry 13:1701–1710.

    PubMed  CAS  Google Scholar 

  • Jaffar, M., Phillips, R. M., Williams, K. J., Mrema, I., Cole, C., Wind, N. S., Ward, T. H., Stratford, I. J., and Patterson, A. V. 2003. 3-substituted-5-aziridinyl-1-methylindole-4,7-diones as NQO1-directed antitumouragents: mechanism of activation and cytotoxicity in vitro. Biochem. Pharmacol. 66:1199–1206.

    PubMed  CAS  Google Scholar 

  • Jaiswal, A. K. 1994. Human NAD(P)H:quinone oxidoreductase2. Gene structure, activity, and tissue-specific expression. J. Biol. Chem. 269:14502–14508.

    PubMed  CAS  Google Scholar 

  • Jaiswal, A. K., Burnett, P., Adesnik, M., and McBride, O. W. 1990. Nucleotide and deduced amino acid sequence of a human cDNA (NQO2) corresponding to a second member of the NAD(P)H:quinone oxidoreductase gene family. Extensive polymorphism at the NQO2 gene locus on chromosome 6. Biochemistry 29:1899–1906.

    PubMed  CAS  Google Scholar 

  • Jamieson, D., Tung, A. T., Knox, R. J., and Boddy, A. V. 2006 Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor. Br. J. Cancer 95:1229–33.

    PubMed  CAS  Google Scholar 

  • Jarabak, J., and Harvey, R. G. 1993. Studies on three reductases which have polycyclic aromatic hydrocarbon quinones as substrates. Arch. Biochem. Biophys. 303:394–401.

    PubMed  CAS  Google Scholar 

  • Keeney, P. M., Xie, J., Capaldi, R. A., Bennett, J. P. 2006. Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J. Neurosci. 26:5256–5264.

    PubMed  CAS  Google Scholar 

  • Kelland, L. R., Sharp, S. Y., Rogers, P. M., Myers, T. G., and Workman, P. 1999. DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J. Natl. Cancer Inst. 91:1940–1949.

    PubMed  CAS  Google Scholar 

  • King, C. L., Wong, S. K., and Loo, T. L. 1984. Alkylation of DNA by the new anticancer agent 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (AZQ). Eur. J. Cancer Clin. Oncol. 20:261–264.

    PubMed  CAS  Google Scholar 

  • Knox, R. J., Jenkins, T. C., Hobbs, S. M., Chen, S., Melton, R. G., and Burke, P. J. 2000. Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug therapy. Cancer Res. 60:4179–4186.

    PubMed  CAS  Google Scholar 

  • Komiyama, T., Kikuchi, T., and Sugiura, Y. 1986. Interactions of anticancer quinone drugs, aclacinomycin A, adriamycin, carbazilquinone, and mitomycin C, with NADPH-cytochrome P-450 reductase, xanthine oxidase and oxygen. J. Pharmacobiodyn. 9:651–664.

    PubMed  CAS  Google Scholar 

  • Kumagai, Y., Midorikawa, K., Nakai, Y., Yoshikawa, T., Kushida, K., Homma-Takeda, S., and Shimojo, N. 1998. Inhibition of nitric oxide formation and superoxide generation during reduction of LY83583 by neuronal nitric oxide synthase. Eur. J. Pharmacol. 360:213–218.

    PubMed  CAS  Google Scholar 

  • Kwiek, J. J., Haystead, T. A., and Rudolph, J. 2004. Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry 43:4538–4547.

    PubMed  CAS  Google Scholar 

  • Levay, G., Ross, D., and Bodell, W. J. 1993. Peroxidase activation of hydroquinone results in the formation of DNA adducts in HL-60 cells, mouse bone marrow macrophages and human bone marrow. Carcinogenesis 14:2329–2334.

    PubMed  CAS  Google Scholar 

  • Lenaz, G., Fato, R., Genova, M. L., Bergamini, C., Bianchi, C., and Biondi, A. 2006. Mitochondrial Complex I: structural and functional aspects. Biochim. Biophys. Acta 2006 1757:1406–20.

    CAS  Google Scholar 

  • Li, R., Bianchet, M. A., Talalay, P., and Amzel, L. M. 1995. The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction. Proc. Natl. Acad. Sci. U.S.A. 92:8846–8850.

    PubMed  CAS  Google Scholar 

  • Liebler, D. C., Kaysen. K. L., and Kennedy, T. A. 1989. Redox cycles of vitamin E: hydrolysis and ascorbic acid dependent reduction of 8a-(alkyldioxy)tocopherones. Biochemistry 28:9772–9777.

    PubMed  CAS  Google Scholar 

  • Linas, S. L., Whittenburg, D., and Repine, J. E. 1990. Role of xanthine oxidase in ischemia/reperfusion injury. Am. J. Physiol. 258:F711–F716.

    PubMed  CAS  Google Scholar 

  • Lind, C., Cadenas, E., Hochstein, P., and Ernster, L. 1990. DT-diaphorase: purification, properties, and function. Methods Enzymol. 186:287–301.

    PubMed  CAS  Google Scholar 

  • Long, D. J., and Jaiswal, A. K. 2000. Mouse NRH:quinone oxidoreductase (NQO2): cloning of cDNA and gene- and tissue-specific expression. Gene. 252:107–117.

    PubMed  CAS  Google Scholar 

  • Long, D. J., Iskander, K., Gaikwad, A., Arin, M., Roop, D. R., Knox, R., Barrios, R., and Jaiswal, A. K. 2002. Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity. J. Biol. Chem. 277:46131–46139.

    PubMed  CAS  Google Scholar 

  • Lusthof, K. J., Richter, W., de Mol, N. J., Janssen, L. H., Verboom, W., and Reinhoudt, D. N. 1990. Reductive activation of potential antitumor bis(aziridinyl)benzoquinones by xanthine oxidase: competition between oxygen reduction and quinone reduction. Arch. Biochem. Biophys. 277:137–142.

    PubMed  CAS  Google Scholar 

  • Lusthof, K.J., de Mol, N. J., Richter, W., Janssen, L. H., Butler, J., Hoey, B. M., Verboom W. and Reinhoudt, D. N. 1992. Redox cycling of potential antitumor aziridinyl quinones. Free Radic. Biol. Med. 13:599–608.

    Google Scholar 

  • Lyn-Cook, B. D, Yan-Sanders, Y., Moore, S., Taylor, S., Word, B., and Hammons, G. J. 2006. Increased levels of NAD(P)H: quinone oxidoreductase 1 (NQO1) in pancreatic tissues from smokers and pancreatic adenocarcinomas: a potential biomarker of early damage in the pancreas. Cell Biol. Toxicol. 22:73–80.

    PubMed  CAS  Google Scholar 

  • Maliepaard, M., Wolfs, A., Groot, S. E., de Mol, N. J., and Janssen, L. H. 1995. Indoloquinone EO9: DNA interstrand cross-linking upon reduction by DT-diaphorase or xanthine oxidase. Br. J. Cancer 71:836–839.

    Google Scholar 

  • Marsh, W. S., Garretson, A. L., and Wesel, E. M. 1961. Streptonigrin, an antitumor agent produced by strains of Streptomyces flocculus. I. Microbiological studies. Antibiot. Chemother. 11:151–157.

    PubMed  CAS  Google Scholar 

  • Masters, B. S., Bilimoria, M. H., Kamin, H., and Gibson, Q. H. 1965. The mechanism of 1- and 2-electron transfers catalyzed by reduced triphosphopyridine nucleotide-cytochrome c reductase. J. Biol. Chem. 240:4081–4088.

    PubMed  CAS  Google Scholar 

  • McCord, J. M. 1985. Oxygen-derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312:159–163.

    PubMed  CAS  Google Scholar 

  • Mishin, V., Pokrovsky, A., and Lyakhovich, V. V. 1976. Interactions of some acceptors with superoxide anion radicals formed by the NADPH-specific flavoprotein in rat liver microsomal fractions. Biochem. J. 154:307–310.

    PubMed  CAS  Google Scholar 

  • Moran, J. L., Siegel, D., and Ross, D. 1999. A potential mechanism underlying the increased susceptibility of individuals with a polymorphism in NAD(P)H:quinone oxidoreductase 1 (NQO1) to benzene toxicity. Proc. Natl. Acad. Sci. U.S.A. 96:8150–8155.

    PubMed  CAS  Google Scholar 

  • Munday, R. 2000. Autoxidation of naphthohydroquinones: effects of pH, naphthoquinones and superoxide dismutase. Free Rad. Res. 32:245–253.

    CAS  Google Scholar 

  • Munday, R. 2004. Activation and detoxification of naphthoquinones by NAD(P)H:quinone oxidoreductase. Methods. Enzymol. 382:364–380.

    PubMed  CAS  Google Scholar 

  • Munday, R., Smith, B. L., and Munday, C. M. 1998. Effects of butylated hydroxyanisole and dicoumarol on the toxicity of menadione to rats. Chem. Biol. Interact. 108:155–170.

    PubMed  CAS  Google Scholar 

  • Munday, R., Smith, B. L., and Munday, C. M. 1999a. Effect of butylated hydroxyanisole on the toxicity of 2-hydroxy-1,4-naphthoquinone to rats. Chem. Biol. Interact. 117:241–256.

    CAS  Google Scholar 

  • Munday, R., Smith, B. L., and Munday, C. M. 1999b. Effect of inducers of DT-diaphorase on the toxicity of 2-methyl- and 2-hydroxy-1,4-naphthoquinone to rats. Chem. Biol. Interact. 123:219–237.

    CAS  Google Scholar 

  • Mustacich, D., and Powis, G. 2000. Thioredoxin Reductase. Biochem. J.346:1–8.

    Google Scholar 

  • Naylor, M. A., Swann, E., Everett, S. A., Jaffar, M., Nolan, J., Robertson, N., Lockyer, S. D., Patel, K. B., Dennis, M. F., Stratford, M. R, Wardman, P., Adams, G. E., Moody, C. J., and Stratford, I. J. 1998. Indolequinone antitumor agents: reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia-selective cytotoxicity in vitro. J. Med. Chem. 41:2720–31.

    PubMed  CAS  Google Scholar 

  • Nemeikaite-Ceniene, A., Sarlauskas, J., Anusevicius, Z., Nivinskas, H., and Cenas, N. 2003. Cytotoxicity of RH1 and related aziridinylbenzoquinones: involvement of activation by NAD(P)H:quinone oxidoreductase (NQO1) and oxidative stress. Arch Biochem. Biophys. 416:110–118.

    PubMed  CAS  Google Scholar 

  • Nishino, T. 1994. The conversion of xanthine dehydrogenase to xanthine oxidase and the role of the enzyme in reperfusion injury. J. Biochem. (Tokyo). 116:1–6.

    CAS  Google Scholar 

  • Nosjean, O., Ferro, M., Coge, F., Beauverger, P., Henlin, J. M., Lefoulon. F., Fauchere. J. L., Delagrange, P., Canet, E., and Boutin, J. A. 2000. Identification of the melatonin-binding site MT3 as the quinone reductase 2. J. Biol. Chem. 275:31311–31317.

    PubMed  CAS  Google Scholar 

  • Ollinger, K., Buffinton, G. D., Ernster, L., and Cadenas, E. 1990. Effect of superoxide dismutase on the autoxidation of substituted hydro- and semi-naphthoquinones. Chem. Biol. Interact. 73:53–76.

    PubMed  CAS  Google Scholar 

  • Ough, M., Lewis, A., Bey, E. A., Gao, J., Ritchie, J. M., Bornmann, W., Boothman, D. A., Oberley, L. W., and Cullen, J. J. 2005. Efficacy of beta-lapachone in pancreatic cancer treatment: exploiting the novel, therapeutic target NQO1. Cancer Biol. 4:95–102.

    CAS  Google Scholar 

  • O’Brien, P. J. 1991. Molecular mechanisms of quinone cytotoxicity. Chem. Biol. Interact. 80:1–41.

    PubMed  Google Scholar 

  • Pan, S. S., and Bachur, N. R. 1980. Xanthine oxidase catalyzed reductive cleavage of anthracycline antibiotics and free radical formation. Mol. Pharmacol. 17:95–99.

    PubMed  CAS  Google Scholar 

  • Pan, S. S., and Gonzalez, H. 1990. Mitomycin antibiotic reductive potential and related pharmacological activities. Mol. Pharmacol. 37:966–970.

    PubMed  CAS  Google Scholar 

  • Pan, S. S., and Iracki, T. 1988. Metabolites and DNA adduct formation from flavoenzyme-activated porfiromycin. Mol. Pharmacol. 34:223–228.

    PubMed  CAS  Google Scholar 

  • Pan, S. S., Andrews, P. A., Glover, C. J., and Bachur, N. R. 1984. Reductive activation of mitomycin C and mitomycin C metabolites catalyzed by NADPH-cytochrome P-450 reductase and xanthine oxidase. J. Biol. Chem. 259:959–966.

    PubMed  CAS  Google Scholar 

  • Pavlidis, N., Hanauske, A. R., Gamucci, T., Smyth, J., Lehnert, M., te Velde, A., Lan, J., and Verweij, J. 1996. A randomized phase II study with two schedules of the novel indoloquinone EO9 in non-small-cell lung cancer: a study of the EORTC Early Clinical Studies Group (ECSG). Ann. Oncol. 7:529–531.

    PubMed  CAS  Google Scholar 

  • Petlicki, J., and van de Ven, T. G. M. 1998. The equilibrium between the oxidation of hydrogen peroxide by oxygen and the dismutation of peroxyl or superoxide radicals in aqueous solutions in contact with oxygen. J. Chem. Soc. Faraday Transactions 94:2763–2769.

    Google Scholar 

  • Petrone, W. F., English, D. K., Wong, K., and McCord, J. M. 1980. Free radicals and inflammation: superoxide-dependent activation of a neutrophil chemotactic factor in plasma. Proc. Natl. Acad. Sci. U.S.A. 77:1159–1163.

    PubMed  CAS  Google Scholar 

  • Phillips, A. H., and Langdon, R. G. 1962. Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J. Biol. Chem. 237:2652–2660.

    PubMed  CAS  Google Scholar 

  • Pink, J. J., Planchon, S. M., Tagliarino, C., Varnes, M. E., Siegel, D., and Boothman, D. A. 2000. NAD(P)H:Quinone oxidoreductase activity is the principal determinant of beta-lapachone cytotoxicity. J. Biol. Chem. 275:5416–5424.

    PubMed  CAS  Google Scholar 

  • Planchon, S. M., Wuerzberger, S., Frydman, B., Witiak, D. T,, Hutson, P., Church, D. R., Wilding, G., and Boothman, D. A. 1995. Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: a p53-independent response. Cancer Res. 55:3706–3711.

    PubMed  CAS  Google Scholar 

  • Powers, M. V., and Workman, P. 2006. Targeting of multiple signaling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocr. Relat. Cancer 13:S125-S135.

    PubMed  CAS  Google Scholar 

  • Powis, G. 1987. Metabolism and reactions of quinoid anticancer agents. Pharmacol. Ther. 35:57–162.

    PubMed  CAS  Google Scholar 

  • Powis, G., and Appel, P. L. 1980. Relationship of the single-electron reduction potential of quinones to their reduction by flavoproteins. Biochem. Pharmacol. 29:2567–2572.

    PubMed  CAS  Google Scholar 

  • Pritsos, C. A., and Gustafson, D. L. 1994. Xanthine dehydrogenase and its role in cancer chemotherapy. Oncol. Res. 6:477–481.

    PubMed  CAS  Google Scholar 

  • Radjendirane, V., Joseph, P., Lee, Y. H., Kimura, S., Klein-Szanto, A. J., Gonzalez, F. J., and Jaiswal, A. K. 1998. Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J. Biol. Chem. 273:7382–7389.

    PubMed  CAS  Google Scholar 

  • Reigan, P., Colucci, M. A., Siegel, D., Chiloux, A., Moody, C. J., Ross, D. (2007) Development of indolequinone mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1): NQO1 inhibition and growth inhibitory activity in human pancreatic MIA PaCa-2 cancer cells. Biochemistry. 46:5941–5950.

    Google Scholar 

  • Ris, M. M., and von Wartburg, J. P. 1973. Heterogeneity of NADPH-dependent aldehyde reductase from human and rat brain. Eur. J. Biochem. 37:69–77.

    PubMed  CAS  Google Scholar 

  • Ross, D., and Siegel, D. 2004. NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase), functions and pharmacogenetics. Methods Enzymol. 382:115–144.

    PubMed  CAS  Google Scholar 

  • Ross, D., Beall, H. D., Siegel, D., Traver, R. D., and Gustafson, D. L. 1996. Enzymology of bioreductive drug activation. Br. J. Cancer 27:S1–8.

    CAS  Google Scholar 

  • Ross, D., Beall, H., Traver. R. D., Siegel, D., Phillips, R. M., and Gibson, N. W. 1994. Bioactivation of quinones by DT-diaphorase, molecular, biochemical, and chemical studies. Oncol. Res. 6:493–500.

    PubMed  CAS  Google Scholar 

  • Ross, D., Siegel, D., Beall, H., Prakash, A. S., Mulcahy, R. T., and Gibson, N. W. 1993. DT-diaphorase in activation and detoxification of quinones. Bioreductive activation of mitomycin C. Cancer Metastasis Rev. 12:83–101.

    PubMed  CAS  Google Scholar 

  • Rothman, N., Smith, M. T., Hayes, R. B., Traver, R. D., Hoener, B., Campleman, S., Li, G. L., Dosemeci, M., Linet, M., Zhang, L., Xi, L., Wacholder, S., Lu, W., Meyer, K. B., Titenko-Holland, N., Stewart, J. T., Yin, S., and Ross, D. 1997. Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C>T mutation and rapid fractional excretion of chlorzoxazone. Cancer Res. 57:2839–2842.

    PubMed  CAS  Google Scholar 

  • Sartorelli, A. C. 1988. Therapeutic attack of hypoxic cells of solid tumors: Presidential Address. Cancer Res. 48:775–778.

    PubMed  CAS  Google Scholar 

  • Schlager, J. J., and Powis, G. 1990. Cytosolic NAD(P)H:(quinone-acceptor)oxidoreductase in human normal and tumor tissue: effects of cigarette smoking and alcohol. Int. J. Cancer 45:403–409.

    PubMed  CAS  Google Scholar 

  • Schlosser, M. J., and Kalf, G. F. 1989. Metabolic activation of hydroquinone by macrophage peroxidase. Chem. Biol. Interact. 72:191–207.

    PubMed  CAS  Google Scholar 

  • Schuerch, A. R., and Wehrli, W. 1978. Beta-lapachone, an inhibitor of oncornavirus reverse transcriptase and eukaryotic DNA polymerase-alpha. Inhibitory effect, thiol dependence and specificity. Eur. J. Biochem. 84:197–205.

    PubMed  CAS  Google Scholar 

  • Schulte, T. W., and Neckers, L. M. 1998. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol. 42:273–279.

    CAS  Google Scholar 

  • Schwartz, J. M., and Jaffe, E. R. 1978. Hereditary methemoglobinemia with deficiency of NADH-dehydrogenase. In The Metabolic Basis of Inherited Disease (ed 4), eds. J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, p. 1452. New York: McGraw-Hill.

    Google Scholar 

  • Shen, A. L., Sem, D. S., and Kasper, C. B. 1999. Mechanistic studies on the reductive half-reaction of NADPH-cytochrome P450 oxidoreductase. J. Biol. Chem. 274:5391–5398.

    PubMed  CAS  Google Scholar 

  • Siegel, D., and Ross, D. 2000. Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues. Free Rad. Biol. Med. 29:246–253.

    PubMed  CAS  Google Scholar 

  • Siegel, D., Anwar, A., Winski, S. L., Kepa, J. K., Zolman, K. L., and Ross, D. 2001. Rapid polyubiquitination and proteasomal degradation of a mutant form of NAD(P)H:quinone oxidoreductase 1. Mol. Pharmacol. 59:263–268.

    PubMed  CAS  Google Scholar 

  • Siegel, D., Beall, H., Kasai, M., Arai, H., Gibson, N. W., and Ross, D. 1993. pH-Dependent inactivation of DT-diaphorase by mitomycin C and porfiromycin. Mol. Pharmacol. 44:1128–1134.

    PubMed  CAS  Google Scholar 

  • Siegel, D., Beall, H., Senekowitsch, C., Kasai, M., Arai, H., Gibson, N. W., and Ross, D. 1992. Bioreductive activation of mitomycin C by DT-diaphorase. Biochemistry 31:7879–7885.

    PubMed  CAS  Google Scholar 

  • Siegel, D., Bolton, E. M., Burr, J. A., Liebler, D. C., and Ross, D. 1997. The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular antioxidant. Mol. Pharmacol. 52:300–305.

    PubMed  CAS  Google Scholar 

  • Siegel, D., Gibson, N. W., Preusch, P. C., and Ross, D. 1990. Metabolism of diaziquone by NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase): role in diaziquone-induced DNA damage and cytotoxicity in human colon carcinoma cells. Cancer Res. 50:7293–7300.

    PubMed  CAS  Google Scholar 

  • Siegel, D., Gustafson, D. L., Dehn, D. L., Han, J. Y., Boonchoong, P., Berliner, L. J., and Ross, D. 2004. NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger. Mol. Pharmacol. 65:1238–1247.

    PubMed  CAS  Google Scholar 

  • Sreerama, L., Hedge, M. W., and Sladek, N. E. 1995. Identification of a class 3 aldehyde dehydrogenase in human saliva and increased levels of this enzyme, glutathione S-transferases, and DT-diaphorase in the saliva of subjects who continually ingest large quantities of coffee or broccoli. Clin. Cancer Res. 1:1153–1163.

    PubMed  CAS  Google Scholar 

  • Strassburg, A., Strassburg, C. P., Manns, M. P., and Tukey, R. H. 2002. Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue. Mol. Pharmacol. 61:320–325.

    PubMed  CAS  Google Scholar 

  • Strittmatter, P. 1965. The reaction sequence in electron transfer in the reduced nicotinamide adenine dinucleotide-cytochrome b 5 reductase system. J. Biol. Chem. 240:4481–4487.

    PubMed  CAS  Google Scholar 

  • Sugiura, Y., Kuwahara, J., and Suzuki, T. 1984. DNA interaction and nucleotide sequence cleavage of copper-streptonigrin. Biochim. Biophys. Acta 782:254–261.

    PubMed  CAS  Google Scholar 

  • Sussman, M. S., and Bulkley, G. B. 1990. Oxygen-derived free radicals in reperfusion injury. Methods Enzymol. 186:711–723.

    PubMed  CAS  Google Scholar 

  • Swann, E., Barraja, P., Oberlander, A. M., Gardipee, W. T., Hudnott, A. R., Beall, H. D., and Moody, C. J. 2001. Indolequinone antitumor agents: correlation between quinone structure and rate of metabolism by recombinant human NAD(P)H:quinone oxidoreductase. Part 2. J. Med. Chem. 44:3311–3319.

    PubMed  CAS  Google Scholar 

  • Sydor, J. R., Normant, E., Pien, C. S., Porter, J. R., Ge, J., Grenier, L., Pak, R. H., Ali, J. A., Dembski, M. S., Hudak, J., Patterson, J., Penders, C., Pink, M., Read, M., Sang. J., Woodward, C., Zhang, Y., Grayzel, D. S., Wright, J., Barrett, J. A., Palombella, V. J., Adams, J., and Tong, J. K. 2006. Development of 17-allylamino-17 demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp 90. Proc. Natl. Acad. Sci. U.S.A. 103:17408–17413.

    PubMed  CAS  Google Scholar 

  • Terada, L. S., Willingham, I. R., Rosandich, M. E., Leff, J. A., Kindt, G. W., and Repine, J. E. 1991. Generation of superoxide anion by brain endothelial cell xanthine oxidase. J. Cell. Physiol. 148:191–196.

    PubMed  CAS  Google Scholar 

  • Thomas, D. J., Sadler, A., Subrahmanyam, V. V., Siegel, D., Reasor, M. J., Wierda, D., and Ross, D. 1990. Bone marrow stromal cell bioactivation and detoxification of the benzene metabolite hydroquinone: comparison of macrophages and fibroblastoid cells. Mol. Pharmacol. 37:255–262.

    PubMed  CAS  Google Scholar 

  • Thor, H., Smith, M. T., Hartzell, P., Bellomo, G., Jewell, S. A., and Orrenius, S. 1982. The metabolism of menadione (2-methyl-1,4-naphthoquinone) by isolated hepatocytes. A study of the implications of oxidative stress in intact cells. J. Biol. Chem. 257:12419–12425.

    PubMed  CAS  Google Scholar 

  • Traver, R. D., Siegel, D., Beall, H. D., Phillips, R. M., Gibson, N. W., Franklin, W. A., and Ross, D. 1997. Characterization of a polymorphism in NAD(P)H:quinone oxidoreductase (DT-diaphorase). Br. J. Cancer 75:69–75.

    PubMed  CAS  Google Scholar 

  • Vasiliou, V., Ross, D., and Nebert, D. W. 2006. Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family. Hum. Genom. 2:329–335.

    CAS  Google Scholar 

  • Verma RP. 2006. Anti-cancer activities of 1,4-naphthoquinones: a QSAR study. Anticancer Agents Med. Chem. 6:489–499.

    PubMed  CAS  Google Scholar 

  • Vermilion, J. L., and Coon, M. J. 1978 Purified liver microsomal NADPH-cytochrome P-450 reductase. Spectral characterization of oxidation–reduction states. J. Biol. Chem. 253:2694–2704.

    PubMed  CAS  Google Scholar 

  • Vienozinskis, J., Butkus, A., Cenas, N. and Kulys, J.1990. The mechanism of the quinone reductase reaction of pig heart lipoamide dehydrogenase. Biochem. J. 269:101–105.

    Google Scholar 

  • Wang, Z, Hsieh, T. C., Zhang, Z., Ma, Y., and Wu, J. M. 2004. Identification and purification of resveratrol targeting proteins using immobilized resveratrol affinity chromatography. Biochem. Biophys. Res. Commun. 323:743–749.

    CAS  Google Scholar 

  • Wardman, P. 2001. Electron transfer and oxidative stress as key factors in the design of drugs selectively active in hypoxia. Curr. Med. Chem. 8:739–761.

    PubMed  CAS  Google Scholar 

  • Wermuth, B. 1981. Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. J. Biol. Chem. 256:1206–1213.

    PubMed  CAS  Google Scholar 

  • Wermuth, B., Bohren, K. M., Heinemann, G., and von Wartburg, J. P., Gabbay, K. H. 1988. Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and amino acid sequence of the encoded protein. J. Biol. Chem. 263:16185–16188.

    PubMed  CAS  Google Scholar 

  • Wermuth, B., Burgisser, H., Bohren, K., and von Wartburg, J. P. 1982. Purification and characterization of human-brain aldose reductase. Eur. J. Biochem. 127:279–284.

    PubMed  CAS  Google Scholar 

  • Wermuth, B., Platts, K. L., Seidel, A., and Oesch, F. 1986. Carbonyl reductase provides the enzymatic basis of quinone detoxication in man. Biochem. Pharmacol. 35:1277–1282.

    CAS  Google Scholar 

  • White, J. R. 1977. Streptonigrin-transition metal complexes: binding to DNA and biological activity. Biochem. Biophys. Res. Commun. 77:387–391.

    CAS  Google Scholar 

  • Williams, C. H. Jr, and Kamin, H. 1962. Microsomal triphosphopyridine nucleotide-cytochrome c reductase of liver. J. Biol. Chem.. 237:587–595.

    PubMed  CAS  Google Scholar 

  • Winski, S. L., Hargreaves, R. H., Butler, J., and Ross, D. 1998. A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: identification of a new aziridinylbenzoquinone, RH1, as a NQO1-directed antitumor agent. Clin. Cancer Res. 4:3083–3088.

    PubMed  CAS  Google Scholar 

  • Winski, S. L., Swann, E., Hargreaves, R. H., Dehn, D. L., Butler, J., Moody, C. J., and Ross, D. 2001. Relationship between NAD(P)H:quinone oxidoreductase 1 (NQO1) levels in a series of stably transfected cell lines and susceptibility to antitumor quinones. Biochem. Pharmacol. 61:1509–1516.

    PubMed  CAS  Google Scholar 

  • Wirth, H., and Wermuth, B. 1992. Immunohistochemical localization of carbonyl reductase in human tissues. J. Histochem. Cytochem. 40:1857–63.

    PubMed  CAS  Google Scholar 

  • Wu, K., Knox, R., Sun, X. Z., Joseph, P., Jaiswal, A. K., Zhang, D., Deng, P. S., and Chen, S. 1997. Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase. Arch. Biochem. Biophys. 347:221–228.

    PubMed  CAS  Google Scholar 

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The authors are supported by H.H.S. grants CA51210, CA114441, E09554, and NS44613.

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Siegel, D., Reigan, P., Ross, D. (2008). One- and Two-Electron-Mediated Reduction of Quinones: Enzymology and Toxicological Implications. In: Elfarra, A. (eds) Advances in Bioactivation Research. Biotechnology: Pharmaceutical Aspects, vol IX. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77300-1_7

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