The role of NAD(P)H oxidoreductase (DT-Diaphorase) in the bioactivation of quinone-containing antitumor agents: A review

Free Radical Biology and Medicine

Volumn 29, Issue 3-4, 2000, Pages 263-275

  Gutierrez, Peter L ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Adriamycin; Anthraquinones; Diaziquone; DT Diaphorase; Free radicals; Indoloquinone E09; Menadione; Mitomycin C; Napthazarin

Indexed keywords

ANTINEOPLASTIC AGENT; DIHYDROLIPOAMIDE DEHYDROGENASE; DOXORUBICIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE);

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; DRUG ACTIVATION; DRUG PROTEIN BINDING; ELECTRON TRANSPORT; ENZYME ACTIVITY; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALIA;

EID: 0033800627     PISSN: 08915849     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0891-5849(00)00314-2     Document Type: Article

References (117)

1. Iyanagi T., Yamazaki I. One electron-transfer reactions in biochemical systems. III. One-electron reduction of quinones by microsomal flavin enzymes. Biochem. Biophys. Acta. 172:1969;370-381.
2. Iyanagi T., Yamazaki I. One-electron reductions in biochemical systems. V. Difference in the mechanism of quinone reduction by the NADH dehydrogenase and the NAD(P)H dehydrogenase (DT-Diaphorase). Biochim. Biophys. Acta. 216:1970;282-294.
3. Nakamura M., Yamazaki I. One-electron transfer reactions in biochemical systems. VII. Changes in electron outlets in milk xanthine oxidase. Biochim. Biophys. Acta. 327:1973;247-256.
4. Nakamura M., Yamazaki I. One-electron transfer reactions in biochemical systems. VI. Changes in electron transfer mechanism of lipoamide deydrogenase by modification of sulfhydryl groups. Biochim. Biophys. Acta. 267:1972;249-257.
5. Yamazaki, I. Free radicals in enzyme-substrate reactions. In: Pryor, W. A., ed. Free radicals in biology, Vol. III. New York: Academic Press; 1977:183-215.
6. Lin A.J., Cosby L.A., Shanksky C.W., Sartorelli A.C. Potential bioreductive alkylating agents. 1. Benzoquinone derivatives. J. Med. Chem. 15:1972;1247-1252.
7. Powis G. Metabolism and reactions of quinoid anticancer agents. Pharmacol. Ther. 35:1987;57-162.
8. Cadenas E. Antioxidant and prooxidant functions of DT-Diaphorase in quinone metabolism. Biochem. Pharmacol. 49:1995;127-140.
9. Ernster L. DT-Diaphorase. Methods Enzymol. 10:1967;309-317.
10. 1 (DT-Diaphorase) messenger RNA lacking the putative quinone substrate binding site is present in human normal and tumor tissues. Cancer Res. 55:1995;2542-2547.
11. Schlager J.J., Hoerl B.J., Riebow J., Scott D.P., Gasdaska P., Scott R.E., Powis G. Increased NAD(P)H (quinone-acceptor) oxidoreductase activity is associated with density-dependent growth inhibition of normal but not transformed cells . Cancer Res. 53:1993;1338-1342.
12. Gordon G.B., Prochaska H.J., Yang L.Y.-S. Induction of NAD(P)H quinone reductase in human peripheral blood lymphocytes . Carcinogenesis. 12:1991;2393-2396.
13. Schlager J.J., Powis G. Cytosolic NAD(P)H:(quinone-acceptor) oxidoreductase in human normal and tumor tissue effects of cigarette smoking and alcohol . Int. J. Cancer. 45:1990;403-409.
14. 1) gene in tumor cells compared to normal cells of the same origin . Biochem. Pharmacol. 42:1991;1021-1027.
15. Sreerama L., Sladek N.E. Overexpression of glutathione S-transferases, DT-Diaphorase and an apparently tumour-specific cytosolic class-3 aldehyde dehydrogenase by warthin tumours and mucoepidermoid carcinomas of the human parotid gland. Archs. Oral Biol. 41:1996;597-605.
16. 5 reductase in human lung and breast tumours. Br. J. Cancer. 76:1997;923-929.
17. Riley R.J., Workman P. DT-Diaphorase and cancer chemotherapy. Biochem. Pharmacol. 43:1992;1657-1669.
18. Ross D., Siegel D., Beall H., Prakash A.S., Mulcahy R.T., Gibson N.W. DT-Diaphorase in activation and detoxification of quinones bioreductive activation of mitomycin C . Cancer Metastasis Rev. 12:1993;83-101.
19. Benson A.M., Hunkeler M.J., Talalay P. Increase of NAD(P)H quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity . Proc. Natl. Acad. Sci. USA. 77:1980;5216-5220.
20. Prestera T., Zhang Y., Spencer S.R., Wilczak C.A., Talalay P. The electrophile counter attack response protection against neoplasia and toxicity . Adv. Enzyme Regul. 33:1993;281-296.
21. Beyer R.E., Segura-Aguilar J.E., Ernster L. The anticancer enzyme DT-Diaphorase is induced selectively in liver during ascites hepakonia growth. Anticancer Res. 8:1988;233-238.
22. Doherty G.P., Leith M.K., Wang X., Curphey T.J., Begleiter A. Induction of DT-Diaphorase by 1,2-dithiole-3-thiones in human tumour and normal cells and effect on anti-tumour activity of bioreductive agents. Br. J. Cancer. 77:1996;1241-1252.
23. Begleiter, A.; Leith, M. K.; Curphey, T. J. Induction of DT-Diaphorase by 1,2-dithiole-3-thione and increase of antitumour activity of bioreductive agents. Br. J. Cancer 27(Suppl.):S9-S14; 1996.
24. Sreerama L., Hedge M.W., Sladek N.E. Identification of a class 3 aldehyde dehydrogenase in human saliva and increased levels of this enzyme, glutathione S-transeferases, and DT-Diaphorase in the saliva of subjects who continually ingest large quantities of coffee or broccoli. Clin. Cancer Res. 1:1995;1153-1163.
25. Lind C., Hoshstein P., Ernster L. DT-Diaphorase as a quinone reductase a cellular control device against semiquinone and superoxide radical formation . Arch. Biochem. Biophys. 216:1982;178-185.
26. Lind C. Formation of benzo[a]pyrene-3,6-quinol mono- and diglucuronides in rat liver microsomes. Arch. Biochem. Biophys. 240:1985;226-235.
27. Munday R. Autoxidation of naphthohydroquinones effects of metals, chelating agents and superoxide dismutase . Free Radic. Biol. Med. 22:1997;689-695.
28. Munday R. Inhibition of naphthohydroquinone autoxidation by DT-Diaphorase (NAD(P)H [quinone acceptor] oxidoreductase) . Redox Rep. 3:1997;189-196.
29. Nutter L.M., Ngo E.O., Fisher G.R., Gutierrez P.L. DNA strand scission and free radical production in menadione-treated cells correlation with cytotoxicity and role of NADPH quinone acceptor oxidoreductase . J. Biol. Chem. 267:1988;17981-17986.
30. Mossoba M.M., Alizadeh M., Gutierrez P.L. Mechanism for the reductive activation of Diaziquone. J. Pharm. Sci. 74:1985;1249-1254.
31. Wallin R. Adriamycin and DT-Diaphorase. Cancer Lett. 30:1986;97-101.
32. Goren M.P., Ahmed N.K., Tereba A. Use of somatic cell hybrids to analyze role of specific enzymes in daunorubicin cytotoxicity. Cancer Res. 47:1987;1924-1929.
33. Galaris D., Rydstom J. Enzyme reduction by daunorubicin in neonatal heart cells in culture. Biochem. Biophys. Res. Commun. 110:1983;364-370.
34. Fisher G.R., Patterson L.H., Gutierrez P.L. A comparison of free radical formation by quinone anti-tumour agents in MCF-7 cells and the role of NAD(P)H (quinone-acceptor) oxidoreductase (DT-Diaphorase). Chem. Biol. Interact. 88:1993;137-153.
35. Brunton V.G., Steele G., Lewis A.D., Workman P. Geldanamycin-induced cytotoxicity in human colon-cancer cell lines evidence against the involvement of c-Src or DT-Diaphorase . Cancer Chemother. Pharmacol. 41:1998;417-422.
36. Hajos A.K.D., Winston G.W. Dinitropyrene nitroreductase activitiy of purified NAD(P)H-quinone oxidoreductase role in rat liver cytosol and induction by Aroclor-1254 treatment . Carcinogenesis. 12:1991;697-702.
37. Šarlauskas J., Dičkancaitė E., Nemeikaitė A., Anusevičius Ž., Nivinskas H., Segura-Aguilar J., Čnasė N. Nitrobenzimidazoles as substrates for DT-Diaphorase and redox cycling compounds their enzymatic reactions and cytotoxicity . Arch. Bioch Biophys. 346:1997;219-229.
38. Knox R.J., Freidlos F., Boland M.P. The bioactivation of CB 1954 and its use as a prodrug in antibody-directed enzyme prodrug therapy (ADEPT). Metastasis Rev. 12:1993;195-212.
39. Khan A.H., Ross W.C.J. Tumour-growth inhibitory nitrophenylaziridines and related compounds structure-activity relationships. II . Chem. Biol. Interact. 4:1972;11-12.
40. Roberts J.J., Friedlos F., Knox R.B. CB (2,4-dinitro-5-aziridinyl benzamide) becomes a DNA interstrand crosslinking agent in Walker tumour cells. Biochem. Biophys Res. Commun. 140:1986;1073-1078.
41. Knox R.J., Friedlos F., Jarman M., Roberts J.J. A new cytotoxic, DNA interstrand crosslinking agent, 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide, is formed from 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by a nitroreductase enzyme in Walker carcinoma cells. Biochem. Pharmacol. 37:1988;4661-4669.
42. Boland M.P., Knox R.J., Roberts J.J. The differences in kinetics of rat and human DT diaphorase result in a differential sensitivity of derived cell lines to CB 1954 (5-(aziridin-1-y1)-2,4-dinitrobenzamide). Biochem. Pharmacol. 41:1991;867-875.
43. Khan, A. H.; Ross, W. C. J. Tumour-growth inhibitory nitrophenylaziridines and related compounds: structure-activity relationships. Chem. Biol. Interact. 1:27-47; 1969/70.
44. Cobb L.M., Connors T.A., Elson L.A., Khan A.H., Mitchley B.C.V., Ross W.C.J., Whisson M.E. 2,4-Dinitro-5-ethylene iminobenzamide (CB 1954) a potent and selective inhibitor of the growth of the Walker carcinoma 256 . Biochem. Pharmacol. 18:1969;1519-1527.
45. Knox R.J., Boland M.P., Friedlos F., Coles B., Southan C., Roberts J.J. The nitroreductase enzyme in Walker cells that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) to 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2). Biochem. Pharmacol. 37:1988;4671-4677.
46. Nemeikaiteè A., Čènas N. The changes of prooxidant and antioxidant enzyme activities in bovine leukemia virus-transformed cells. FEBS Lett. 326:1993;65-68.
47. Čènas N., Čènas A., Dičkancaitè E., Žilvinas A., Nivinskas H., Bironaitè D. The toxicity of aromatic nitrocompounds to bovine leukemia virus-transformed fibroblasts the role of single-electron reduction . Biochim. Biophys. Acta. 1268:1995;159-164.
48. Anusevicius Z., Soffers A.E.M.F., Cénas N., Sarlaukas J., Segura-Aguilar J., Rietjens I.M.C.M. Quantitative structure activity relationships for the conversion of nitrobenzimidazoles by DT-diaphorase implications for the kinetic mechanism . FEBS Lett. 427:1998;325-329.
49. Nguyen B., Gutierrez P.L. Mechanism(s) for the metabolism of mitoxantrone electron spin resonance and electrochemical studies . Chem. Biol. Interact. 74:1990;139-162.
50. Fisher G.R., Gutierrez P.L., Oldcorne M.A., Patterson L.H. NAD(P)H (quinone acceptor) oxidoreductase (DT-Diaphorase)-mediated two-electron reduction of anthraquinone-based antitumor agents and generation of hydroxyl radicals. Biochem. Pharmacol. 43:1992;575-585.
51. Faulds D., Balfour J.A., Chrisp P., Langtry H.D. Mitoxantrone a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer . Drugs. 41:1991;400-449.
52. Islam S.A., Neidle S., Gandecha B.M., Patridge M., Patterson L.H., Brown J.R. Comparative computer graphics and solution studies of the DNA interaction of substituted anthraquinones based on doxorubicin and mitozantrone. J. Med. Chem. 28:1985;857-864.
53. Fisher G.R., Brown J.R., Patterson L.H. Redox cycling in MCF-7 human breast cancer cells by antitumor agents basedon mitoxantrone. Free Radic. Res. Commun. 7:1989;221-226.
54. Fisher G.R., Brown J.R., Patterson L.H. Involvement of hydroxyl radical formation and DNA strand breakage in the cytotoxicity of anthraquinone antitumor agents. Free Radic. Res. Commun. 11:1990;117-125.
55. 2/M cell cycle arrest and apoptosis. Free Radic. Biol. Med. 24:1998;848-854.
56. Hata R., Sano Y., Sugawara R., Matsume A., Kanamori K., Shima T., Hoshi T. Mitomycin, a new antibiotic from streptomyces I. J. Antibiot. (Tokyo). 9:1956;141-146.
57. Wakaki S., Marumo H., Tomioka K., Shimizu G., Kato E., Kamada H., Kudo S., Fujimoto Y. Isolation of new fractions of antitumor mitomycins. Antibiot. Chemother. 8:1958;228-240.
58. Crooke S.T., Bradner W.T. Mitomycin C a review . Cancer Treat. Rev. 3:1976;121-139.
59. Carter S.K., Crooke S.T. Mitomycin C current status and new developments . 1979;Academic Press, New York.
60. Kumar G.S., Lipman R., Cummings J., Tomasz M. Mitomycin C-DNA adducts generated by DT-diaphorase revised mechanism of the enzymatic reductive activation of mitomycin C . Biochemistry. 27:1988;2608-2614.
61. Cummings J., Spanswick V.J., Tomasz M., Smyth J.F. Enzymology of mitomycin C metabolic activation in tumour tissue implications for enzyme-directed bioreductive drug development . Biochem. Pharmacol. 56:1998;405-414.
62. Ross D., Beall H.D., Siegel D., Traver R.D., Gustafson D.L. Enzymology of bioreductive drug activation. Br. J. Cancer. 74:1996;S1-S8.
63. Cummings J., Spanswick V.J., Smyth J.F. Re-evaluation of the molecular pharmacology of mitomycin C. Eur. J. Cancer. 31A:1995;1928-1933.
64. Adams G.E., Stratford I.J., Edwards H.S., Bremner J.C.M., Cole S. Bioreductive drugs as post-irradiation sensitizers comparison of dual function agents with SR 4233 and the mitomycin C analogue E09 . Int. J. Radiat. Oncol. Biol. Phys. 22:1992;717-720.
65. Bizanek R., Chowdry D., Arai H., Kasai M., Hughes C.S., Sartorelli C., Rockwell S., Tomasz M. Adducts of mitomycin C and DNA in EMT6 mouse mammary tumour cells effects of hypoxia and dicoumarol on adduct formation . Cancer Res. 53:1993;5127-5134.
66. Keys S.R., Fracasso P.M., Heimbrook D.C., Rockwell S., Silger S.G., Sartorelli A.C. Role of NADPH:cytochrome c reductase and DT-diaphorase in the biotransformation of mitomycin C. Cancer Res. 44:1984;5638-5643.
67. Keohane A., Godden J., Stratford I.J., Adams G.E. The effects of three bioreductive drugs (mitomycin C, RSU-1069 and SR 4233) on cell lines selected for their sensitivity to mitomycin C or ionising radiation. Br. J. Cancer. 61:1990;722-726.
68. Beall H.D., Mulcahy R.M., Siegel D., Traver R.D., Gibson N.W., Ross D. Metabolism of bioreductive antitumour compounds by purified rat and human DT-diaphorase. Cancer Res. 54:1994;3196-3201.
69. Plumb J.A., Gerritsen M., Workman P. DT-diaphorase protects cells from the hypoxic cytotoxicity of indoloquinone EO9. Br. J. Cancer. 70:1994;1136-1143.
70. Pan S.-S., Andrews P.A., Glover C.J., Bachur N.R. Reductive activation of mitomycin C and mitomycin C metabolites by NADPH-cytochrome P-450 and xanthine oxidase. J. Biol. Chem. 259:1984;959-966.
71. Gustafson D.L., Pritsos C.A. Kinetics and mechanism of mitomycin C bioactivation by xanthine dehydrogenase under aerobic and anaerobic conditions. Cancer Res. 53:1993;5470-5474.
72. Walton M.I., Suggett N., Workman P. The role of human rodent DT-diaphorase in the reductive metabolism of hypoxic cell cytotoxins. Int. J. Radiat. Oncol. Biol. Phys. 22:1992;643-648.
73. Joseph P., Xu Y., Jaiswal A.K. Non-enzymatic and enzymatic activation of mitomycin C identification of a unique cytosolic activity . Int. J. Cancer. 65:1996;263-271.
74. Siegel D., Gibson N.W., Preusch P.C., Ross D. Metabolism of mitomycin C by DT-diaphorase role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells . Cancer Res. 50:1990;7483-7489.
75. Siegel D., Gibson N.W., Preusch P.A., Ross D. pH-dependent metabolism of mitomycins by DT-diaphorase. Proc. Am. Assoc. Cancer Res. 32:1991;317.
76. Siegel D., Beall H., Senekowitsch C., Kasai M., Arai H., Gibson N.W., Ross D. Bioreductive activation of mitomycin C by DT-diaphorase. Biochemistry. 31:1992;7879-7885.
77. Begleiter A., Robotham E., Lacey G., Leith M.K. Increased sensitivity of quinone resistant cells to mitomycin C. Cancer Lett. 45:1989;173-176.
78. Oostveen E.A., Speckamp W.N. Mitomycin analogues I. Indoloquinones as (potential) bis-alkylating agents. Tetrahedron. 43:1987;255-262.
79. Bailey S.M., Lewis A.D., Knox R.J., Patterson L.H., Fisher G.R., Workman P. Reduction of the indoloquinone anticancer drug EO9 by purified DT-diaphorase a detailed kinetic study and analysis of metabolites . Biochem. Pharmacol. 56:1998;613-621.
80. Butler J., Spanswick V.J., Cummings J. The autoxidation of the reduced forms of EO9. Free Radic. Res. 25:1996;141-148.
81. Adams G.E., Stratford I.J., Edwards H.S., Bremner J.C.M., Cole S. Bioreductive drugs as post-irradiation sensitizers comparison of dual function agents with SR 4233 and the mitomycin C analogue EO9 . Int. J. Radiat. Oncol. Biol. Phys. 22:1992;717-720.
82. Robertson N., Haigh A., Adams G.E., Stratford I.J. Factors affecting sensitivity to EO9 in rodent and tumor cells in vitro DT-diaphorase activity and hypoxia . Eur. J. Cancer. 30A:1994;1013-1019.
83. Smitskamp-Wilms E., Hendriks H.R., Peters G.J. Development, pharmacology, role of DT-diaphorase and prospects of the indoloquinone EO9. Gen. Pharmacol. 27:1996;421-429.
84. Cummings J., Spanswick V.J., Gardiner J., Ritchie A., Smyth J.F. Pharmacological and biochemical determinants of the antitumour activity of the indoloquinone EO9. Biochem. Pharmacol. 55:1998;253-260.
85. Workman P., Walton M.I., Bibby M.C., Double D.A. In vivo response of mouse adenocarcinoma of the colon (MAC) tumors to indoloquinone EO9 correlation with bioreductive enzyme content . Br. J. Cancer. 62:1991;515-516.
86. Pavlidis N., Hanauske A.R., Gamucci T., Smyth J., Lehnert M., Tevelde A., Lan J.A. A randomized phase II study with 2 schedules of the novel indoloquinone-EO9 in non-small-cell lung-cancer a study of the EORTC early clinical-studies group (ECSG) . Annals. Oncol. 7:1996;529-531.
87. Wanders J., Pavlidis N., Gamucci T., Huinink W.W.T., Dirix L., Wolff I., Verweij J. Phase II studies with EO9 in breast, colorectal, gastric, pancreatic and NSCLC. Eur. J. Cancer. 31A:1995;565-565.
88. Bailey S.M., Lewis A.D., Workman P. Involvement of NADPH cytochrome P450 reductase in activation of EO9 to a DNA damaging species . Br. J. Cancer. 69:1994;57.
89. Baily S.M., Lewis A.D., Patterson L.H., Fisher G.R., Workman P. Free radical generation following reduction of EO9 involvement in cytotoxicity . Br. J. Cancer. 67:1993;8.
90. Maliepaard M., Wolfs A., Groot S.E., de Mol N.J., Janssen L.H.M. Indoloquinone EO9, DNA interstrand cross-linking upon reduction by DT-diaphorase or xanthine oxidase. Br. J. Cancer. 71:1995;836-839.
91. Kikuchi T., Sugiura Y., Komiyama T. Generation of semiquinone radical from carbazilquinone by NADPH-cytochrome P-450 reductase. Biochem. Pharmacol. 30:1981;1717-1718.
92. Khan A.H., Driscoll J.S. Potential central nervous system antitumor agents aziridinylbenzoquinones 1 . J. Med. Chem. 19:1976;313-317.
93. Haid M., Khandekar J.D., Christ M., Johnson C.M., Miller S.J., Locker G.Y., Merrill J.M., Reisel H., Hatfield A., Lanzotti V., Stiff P., Shaw J., Krauss S., Showel J., Blough R., Gordon L. Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system a phase II study by the Illinois cancer council . Cancer. 56:1985;1311-1315.
94. Case D.C. Jr, Hayes D.M. Phase II study of aziridinylbenzoquinone in refractory lymphoma. Cancer Treat. Rep. 67:1983;993-996.
95. Gutierrez P.L. Mechanism(s) of bioreductive activation the example of diaziquone (AZQ) . Free Radic. Biol. Med. 6:1989;405-445.
96. Ross D., Siegel D., Gibson N.W., Pacheco D., Thomas D.J., Reasor M., Weirda D. Activation and deactivation of quinones catalysed by DT-diaphorase evidence for bioreductive activation of diaziquone (AZQ) in human tumour cells and detoxification of benzene metabolites in bone marrow stroma . Free Radic. Res. Commun. 8:1990;373-381.
97. Fisher G.R., Gutierrez P.L. The reductive metabolism of diaziquone (AZQ) in the S9 fraction of MCF-7 cells free radical formation and NAD(P)H:quinone-acceptor oxidoreductase (DT-diaphorase) activity . Free Radic. Biol. Med. 10:1991;359-369.
98. Siegel D., Gibson N.W., Preusch P.C., Ross D. 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. 50:1990;7293-7300.
99. Gibson N.W., Hartley J.A., Butler J., Siegel D., Ross D. Relationship between DT-diaphorase-mediated metabolism of a series of aziridinylbenzoquinones and DNA damage and cytotoxicity. Mol. Pharmacol. 42:1992;531-536.
100. Fisher G.R., Donis J., Gutierrez P.L. Reductive metabolism of diaziquone (AZQ) in the S9 fraction of MCF-7 cells. II. Enhancement of the alkylating activity of AZQ by NAD(P)H:quinone-acceptor oxidoreductase (DT diaphorase). Biochem. Pharmacol. 44:1992;1625-1635.
101. Fisher G.R., Gutierrez P.L. Free radical formation and DNA strand breakage during metabolism of diaziquone by NAD(P)H quinone-acceptor oxidoreductase (DT-diaphorase) and NADPH cytochrome c reductase. Free Radic. Biol. Med. 11:1991;597-607.
102. Gutierrez P.L., Fox B.M., Mossoba M.M., Bachur N.R. Free radicals in quinone-containing antitumor agents electrochemical reduction of diaziquone (2,5-diaziridine-3,6-bis(carboethoxyamino)-1,4-benzoquinone) and two analogues . Mol. Pharmacol. 26:1984;582-586.
103. Giulivi C., Cadenas E. Extracellular activation of fluorinated aziridinylbenzoquinone in HT29 cells EPR studies . Chem. Biol. Interact. 113:1998;191-204.
104. Giulivi C., Forlin A., Bellin S., Cadena E. Reactions of halogen-substituted aziridinylbenzoquinones with glutathione formation of diglutathionyl conjugates and semiquinones . Chem. Biol. Interact. 108:1998;137-154.
105. Goin J., Giulivi C., Butler J., Cadenas E. Enzymatic-and thiol- mediated halogen-substituted diaziridinylbenzoquinones redox transitions of the semiquinone and semiquinone thioether species . Free Radic. Biol. Med. 18:1995;525-536.
106. Halinska A., Belej T., O'Brien P.J. Cytotoxic mechanisms of anti-tumour quinones in parental and resistant lymphoblasts. Br. J. Cancer. 27:1996;523-527.
107. Silva J.M., O'Brien P.J. Molecular mechanisms of trenimon-induced cytotoxicity towards resistant L5178Y/HBM10 cells. Int. J. Radiat. Oncol. Biol. Phys. 22:1992;639-642.
108. Begleiter A., Robotham E., Lacey G., Leith M.K. Increased sensitivity of quinone resistant cells to mitomycin C. Cancer Lett. 45:1989;173-176.
109. Doherty G.P., Leith M.K., Wang X., Curphey T.J., Begleiter A. Induction of DT-diaphorase by 1,2-dithiole-3-thiones in human tumour and normal cells and effect on anti-tumour activity of bioreductive agents. Br. J. Cancer. 77:1998;1241-1252.
110. Radjendirane V., Joseph P., Lee Y.-H., Kimura S., Klein-Szanto A.J.P., Gonzalez F.J., Jaiswal A.K. Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J. Biol. Chem. 273:1998;7382-7389.
111. Munday R., Smith B.L., Munday C.M. Effects of butylated hydroxyanisole and dicoumarol on the toxicity of menadione to rats. Chem Biol. Interact. 108:1997;155-170.
112. Tampo Y., Yonaha M. Enzymatic and molecular aspects of the antioxidant effect of menadione in hepatic microsomes. Arch. Biochem. Biophys. 334:1996;163-174.
113. Karczewski J.M., Janny G.P., Peters J.G.P., Noordhoek J. Quinone toxicity in DT-diaphorase-efficient and -deficient colon carcinoma cell lines. Biochem. Pharmacol. 57:1999;27-37.
114. Gutierrez, P. L. The influence of ascorbic acid on the free radical metabolism of xenobiotics: the example of diaziquone. Drug Metab. Rev. 19:319-343; 1988.
115. Ngo E.O., Nutter L.M., Sura T., Gutierrez P.L. Induction of p53 by the concerted actions of aziridine and quinone moieties of diaziquone. Chem. Res. Toxicol. 11:1998;360-368.
116. Qiu X., Cadenas E. The role of NAD(P)H quinone oxidoreductase in quinone-mediated p21 induction in human colon carcinoma cells . Arch. Biochem. Biophys. 346:1997;241-251.
117. Qiu X., Schönthal A.H., Forman H.J., Cadenas E. Induction of p21 mediated by reactive oxygen species formed during the metabolism of aziridinylbenzoquinones by HCT116 cells. J. Biol. Chem. 271:1996;31915-31922.