Exploring the mechanistic aspects of mitomycin antibiotic bioactivation in chinese hamster ovary cells overexpressing NADPH:cytochrome C (P-450) reductase and DT-diaphorase

Advances in Enzyme Regulation

Volumn 38, Issue 1, 1998, Pages 111-133

  Belcourt, Michael F ^a   Hodnick, William F ^a   Rockwell, Sara ^a   Sartorelli, Alan C ^a  

^a YALE CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC ANTIBIOTIC; GLUTATHIONE TRANSFERASE; MITOMYCIN; PORFIROMYCIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE FERRIHEMOPROTEIN REDUCTASE;

ANIMAL; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; BIOTRANSFORMATION; CANCER CHEMOTHERAPY; CELL FRACTIONATION; CELL HYPOXIA; CELL SURVIVAL; CHO CELL; CONFERENCE PAPER; DRUG EFFECT; ELECTRON TRANSPORT; GENETIC TRANSFECTION; GENETICS; HAMSTER; HUMAN; HYPOXIA; METABOLISM; NONHUMAN; PHYSIOLOGY; RAT; SOLID TUMOR;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; BIOTRANSFORMATION; CELL FRACTIONATION; CELL HYPOXIA; CELL SURVIVAL; CHO CELLS; CRICETINAE; ELECTRON TRANSPORT; GLUTATHIONE TRANSFERASE; HUMANS; MITOMYCINS; NAD(P)H DEHYDROGENASE (QUINONE); NADPH-FERRIHEMOPROTEIN REDUCTASE; PORFIROMYCIN; RATS; TRANSFECTION;

ANIMALIA; BACTERIA (MICROORGANISMS); CRICETINAE; CRICETULUS GRISEUS; RODENTIA;

EID: 0031875844     PISSN: 00652571     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0065-2571(97)00009-5     Document Type: Conference Paper

References (96)

1. J. E. MOULDER and S. ROCKWELL, Tumor hypoxia: its impact on cancer therapy, pp. 313-341 in Cancer Metastasis Reviews. (I. J. FIDLER and G. POSTE, eds.). Vol. 5. Martinus Nijhoff, Boston, MA. (1987).
2. A. C. SARTORELLI, Therapeutic attack of hypoxic cells of solid tumors: presidential address, Cancer Res. 48, 775-778 (1988).
3. K. A. KENNEDY, B. A. TEICHER, S. ROCKWELL and A. C. SARTORELLI, The hypoxic tumor cell: a target for selective cancer chemotherapy, Biochem. Pharmacol. 29, 1-8 (1980).
4. R. H. THOMLINSON and L. H. GRAY, The histological structure of some human lung tumors and the possible implications for radiotherapy, Brit. J. Cancer 9, 539-549 (1955).
5. P. VAUPEL, F. KALLINOWSKI and P. OKUNIEFF, Blood flow, oxygen, and nutrient supply, and metabolic microenvironment of human tumors: a review, Cancer Res. 49, 6449-6465 (1989).
6. R. K. JAIN, Determinants of tumor blood flow: a review, Cancer Res. 48, 2641-2658 (1988).
7. S. ROCKWELL, Oxygen delivery: implications for the biology and therapy of solid tumors, Oncol. Res. 9, 383-390 (1997).
8. S. ROCKWELL and J. P. S. KNISELY, Hypoxia and angiogenesis in experimental tumor models: therapeutic implications, pp. 335-360 in Regulation of Angiogenesis, (I. D. GOLDBERG and E. M. ROSEN, eds.). Birkhaus Verlog, Basel, Switzerland (1997).
9. T. Y. REYNOLDS, S. ROCKWELL and P. M. GLAZER, Genetic instability induced by the tumor microenvironment, Cancer Res. 56, 5754-5757 (1996).
10. T. G. GRAEBER, C. OSMANIAN, T. JACKS, D. E. HOUSMAN, C. J. KOCH, S. W. LOWE and A. J. GIACCIA, Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumors, Nature 379, 89-91 (1996).
11. S. D. YOUNG, R. S. MARSHALL and R. P. HILL, Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells, Proc. Natl. Acad. Sci. U.S.A. 85, 9533-9537 (1988).
12. D. M. BRIZEL, S. P. SCULLY, J. M. HARRELSON, L. J. LAYFIELD, J. M. BEAN, L. R. PROSNITZ and M. W. DEWHIRST, Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma, Cancer Res. 56, 941-943 (1996).
13. L. SIMPSON-HERREN and P. E. NOKER, Diversity of penetration of anticancer agents into solid tumors, Cell Prolif. 24, 355-365 (1991).
14. B. A. TEICHER, Physiologic mechanisms of therapeutic resistance. Blood flow and hypoxia, Hematol. Oncol. Clin. North Am. 9, 475-506 (1995).
15. G. C. RICE, C. HOY and R. T. SCHIMKE, Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells, Proc. Natl. Acad. Sci. U.S.A. 83, 5978-5982 (1986).
16. G. C. RICE, V. LING and R. T. SCHIMKE, Frequencies of independent and simultaneous selection of Chinese hamster cells for methotrexate and doxorubicin (adriamycin) resistance, Proc. Natl. Acad. Sci. U.S.A. 84, 9261-9264 (1987).
17. A. C. SARTORELLI, M. F. BELCOURT, W. F. HODNICK, S. R. KEYES, C. A. PRITSOS and S. ROCKWELL, Preferential kill of hypoxic EMT6 mammary tumor cells by the bioreductive alkylating agent porfiromycin, Advan. Enzyme Regul. 35, 117-130 (1995).
18. A. C. SARTORELLI, W. F. HODNICK, M. F. BELCOURT, M. TOMASZ, B. HAFFTY, J. J. FISCHER and S. ROCKWELL, Mitomycin C: a prototype bioreductive agent, Oncol. Res. 6, 501-508 (1994).
19. S. ROCKWELL and A. C. SARTORELLI, Mitomycin C and radiation, pp. 125-139 in Antitumor Drug-Radiation Interactions, (B. T. HILL and A. S. BELLAMY, eds.). CRC Press, Inc., Boca Raton, FL (1990).
20. B. G. HAFFTY, Y. H. SON, C. T. SASAKI, R. PAPAC, D. FISCHER, S. ROCKWELL, A. C. SARTORELLI and J. J. FISCHER, Mitomycin C as an adjunct to postoperative radiation therapy in squamous cell carcinoma of the head and neck: results from two randomized clinical trials, Int. J. Radiat. Oncol. Biol. Phys. 27, 241-250 (1993).
21. J. B. WEISSBERG, R. J. PAPAC, Y. H. SON, D. B. FISCHER, R. LAWRENCE, S. ROCKWELL, A. C. SARTORELLI and J. J. FISCHER, Randomized clinical trial of mitomycin C as an adjunct to radiotherapy in head and neck cancer, Int. J. Radiat. Oncol. Biol. Phys. 17, 3-9 (1989).
22. B. G. HAFFTY, Y. H. SON, M. MOINI, R. PAPAC, D. FISCHER, S. ROCKWELL, A. C. SARTORELLI and J. J. FISCHER, Porfiromycin as an adjunct to radiation therapy in squamous cell carcinoma of the head and neck: results of a phase I clinical trial, Radiat. Oncol. Invest. 1, 297-304 (1994).
23. M. TOMASZ, Mitomycin C: small, fast and deadly (but very selective), Chemistry & Biology 2, 575-579 (1995).
24. S. KUMAR, R. LIPMAN and M. TOMASZ, Recognition of specific DNA sequences by mitomycin C for alkylation, Biochemistry 31, 1399-1407 (1992).
25. H. KOHN, V. LI, P. SCHILTZ and M. TANG, On the origins of the DNA sequence selectivity of mitomycin monoalkylation transformations, J. Am. Chem. Soc. 114, 9218-9220 (1992).
26. S. P. TENG, S. A. WOODSON and D. M. CROTHERS, DNA sequence specificity of mitomycin crosslinking, Biochemistry 28, 3901-3907 (1989).
27. J. T. MILLARD, M. F. WEIDNER, S. RAUCHER and P. B. HOPKINS, Determination of the DNA crosslinking sequence specificity of reductively activated mitomycin C at single nucleotide resolution: deoxyguanosine residues at CpG are cross-linked preferentially, J. Am. Chem. Soc. 112, 3637-3641 (1990).
28. H. BOROWY-BOROWSKI, R. LIPMAN and M. TOMASZ, Recognition between mitomycin C and specific DNA sequences for crosslink formation, Biochemistry 29, 2999-3004 (1990).
29. W. SYZBALSKI and V. N. IYER, Crosslinking of DNA by enzymatic or chemically activated mitomycins and porfiromycins, bifunctionally "alkylating" antibiotics, Fed. Proc. 23, 946-957 (1964).
30. S. R. KEYES, R. LOOMIS, M. P. DIGIOVANNA, C. A. PRITSOS, S. ROCKWELL and A. C. SARTORELLI, Cytotoxicity and DNA crosslinks produced by mitomycin analogs in aerobic and hypoxic EMT6 cells. Cancer Commun. 3, 351-356 (1991).
31. C. S. HUGHES, C. G. IRVIN and S. ROCKWELL, Effect of deficiencies in DNA repair on the toxicity of mitomycin C and porfiromycin to CHO cells under aerobic and hypoxic conditions, Cancer Commun. 3, 29-35 (1991).
32. K. A. KENNEDY, S. G. SLIGAR, L. POLOMSKI and A. C. SARTORELLI, Metabolic activation of mitomycin C by liver microsomes and nuclei, Biochem. Pharmacol. 31, 2011-2016 (1982).
33. T. KOMIYAMA, T. OKI and T. INUI, Activation of mitomycin C and quinone drug metabolism by NADPH-cytochrome P-450 reductase, J. Pharm. Dyn. 2, 407-410 (1979).
34. N. R. BACHUR, S. L. GORDON, M. V. GEE and H. KON, NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals, Proc. Natl. Acad. Sci. U.S.A. 76, 954-957 (1979).
35. C. A. PRITSOS and A. C. SARTORELLI, Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics, Cancer Res. 46, 3528-3532 (1986).
36. T. KOMIYAMA, T. KIKUCHI and Y. SUGIURA, Generation of hydroxyl radical by anticancer quinone drugs, carbazilquinone, mitomycin C, aclacinomycin A and adriamycin, in the presence of NADPH-cytochrome P-450 reductase, Biochem. Pharmacol. 31, 3651-3656 (1982).
37. S-S. PAN, P. A. ANDREWS, C. J. GLOVER and N. R. BACHUR, 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 (1984).
38. S-S. PAN, T. IRACKI and N. R. BACHUR, DNA alkylation by enzyme-activated mitomycin C, Mol. Pharmacol. 29, 622-628 (1986).
39. S. R. KEYES, P. M. FRACASSO, D. C. HEIMBROOK, S. ROCKWELL, S. G. SLIGAR and A. C. SARTORELLI, Role of NADPH:cytochrome c reductase and DT-diaphorase in the biotransformation of mitomycin C, Cancer Res. 44, 5638-5643 (1984).
40. H. F. J. BLIGH, A. BARTOSZEK, C. N. ROBSON, I. D. HICKSON, C. B. KASPER, J. D. BEGGS and C. R. WOLF, Activation of mitomycin C by NADPH:cytochrome P-450 reductase, Cancer Res. 50, 7789-7792 (1990).
41. D. ROSS, H. BEALL, R. D. TRAVER, D. SIEGEL, R. M. PHILLIPS and N. W. GIBSON, Bioactivation of quinones by DT-diaphorase, molecular, biochemical, and chemical studies, Oncol. Res. 6, 493-500 (1994).
42. D. SIEGEL, N. W. GIBSON, P. C. PREUSCH and D. ROSS, Metabolism of mitomycin C by DT-diaphorase: role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells, Cancer Res. 50, 7483-7489 (1990).
43. D. SIEGEL, H. BEALL, C. SENEKOWITSCH, M. KASAI, H. ARAI, N. W. GIBSON and D. ROSS, Bioreductive activation of mitomycin C by DT-diaphorase, Biochemistry 31, 7879-7885 (1992).
44. C. A. PRITSOS, L. L. PARDINI, A. J. ELLIOT and R. S. PARDINI, Relationship between the antioxidant enzyme DT-diaphorase and tumor response to mitomycin C treatment, pp. 713-716 in Oxygen Radicals in Biology and Medicine, (M. G. SIMIC, K. A. TAYLOR, J. F. WARD and C. VON SONNTAG, eds.). Plenum, New York, NY (1989).
45. A. BEGLEITER, E. ROBOTHAM and M. K. LEITH, Role of NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase) in activation of mitomycin C under hypoxia, Mol. Pharmacol. 41, 677-682 (1992).
46. A. BEGLEITER, E. ROBOTHAM, G. LACEY and M. K. LEITH, Increased sensitivity of quinone resistant cells to mitomycin C, Cancer Letters 45, 173-176 (1989).
47. 5 reductase, Cancer Res. 53, 4907-4912 (1993).
48. J. FISHER and R. OLSEN, Mechanistic aspects of mitomycin C activation by flavoprotein transhydrogenases, Develop. Biochem. 21, 240-243 (1982).
49. D. L. GUSTAFSON and C. A. PRITSOS, Bioactivation of mitomycin C by xanthine dehydrogenase from EMT6 mouse mammary carcinoma tumors, J. Natl. Cancer Inst. 84, 1180-1185 (1992).
50. D. L. GUSTAFSON and C. A. PRITSOS, Enhancement of xanthine dehydrogenase mediated mitomycin C metabolism by dicumarol, Cancer Res. 52, 6936-6939 (1992).
51. C. A. PRITSOS and D. L. GUSTAFSON, Xanthine dehydrogenase and its role in caner chemotherapy, Oncol. Res. 6, 477-481 (1994).
52. B. H. XU, V. GUPTA and S. V. SINGH, Characterization of a human bladder cancer cell line selected for resistance to mitomycin C, Int. J. Cancer 58, 686-692 (1994).
53. P. R. HOBAN, M. I. WALTON, C. N. ROBSON, J. GODDEN, I. J. STRATFORD, P. WORKMAN, A. L. HARRIS and I. D. HICKSON, Decreased NADPH: cytochrome P-450 reductase activity and impaired drug activation in a mammalian cell line resistant to mitomycin C under aerobic but not hypoxic conditions, Cancer Res. 50, 4692-4697 (1990).
54. B. H. XU, V. GUPTA and S. V. SINGH, Mechanism of differential sensitivity of human bladder cancer cells to mitomycin C and its analogue, Brit. J. Cancer 69, 242-246 (1994).
55. M. F. BELCOURT, W. F. HODNICK, S. ROCKWELL and A. C. SARTORELLI, Differential toxicity of mitomycin C and porfiromycin in 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 (1996).
56. M. F. BELCOURT, W. F. HODNICK, S. ROCKWELL and A. C. SARTORELLI, Bioactivation of mitomycin antibiotics by aerobic and hypoxic Chinese hamster ovary cells overexpressing DT-diaphorase, Biochem. Pharmacol. 51, 1669-1678 (1996).
57. G. URLAUB and L. A. CHASIN, Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity, Proc. Natl. Acad. Sci. U.S.A. 77, 4216-4220 (1980).
58. S. YAMANO, T. AOYAMA, O. W. MCBRIDE, J. P. HARDWICK, H. V. GELBOIN and F. J. GONZALEZ, Human NADPH-P450 oxidoreductase: complementary DNA cloning, sequence, and vaccinia virus-mediated expression and localization of the CYPOR gene to chromosome 7, Mol. Pharmacol. 35, 83-88 (1989).
59. J. A. ROBERTSON, H-C. CHEN and D. W. NEBERT, NAD(P)H:menadione oxidoreductase, J. Biol. Chem. 261, 15794-15799 (1986).
60. G. L. FORREST, J. QIAN, J-X. MA, W. D. KAPLAN, S. AKMAN, J. DOROSHOW and S. CHEN, Rat liver NAD(P)H:quinone oxidoreductase: cDNA expression and site-directed mutagenesis, Biochem. Biophys. Res. Commun. 169, 1087-1093 (1990).
61. M. KOZAK, The scanning model for translation: an update, J. Cell Biol. 108, 229-241 (1989).
62. J. SAMBROOK, E. F. FRITSCH and T. MANIATIS, in Molecular Cloning: a Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY (1989).
63. L. ERNSTER, DT-diaphorase, Methods Enzymol. 10, 309-317 (1967).
64. Y. YASUKOCHI and B. S. S. MASTERS, Some properties of a detergent-solubilized NADPH-cytochrome c (cytochrome P-450) reductase purified by biospecific affinity chromatography, J. Biol. Chem. 251, 5337-5344 (1976).
65. 5 reductase of rabbit erythrocytes, J. Biochem. (Tokyo) 91, 1467-1477 (1982).
66. F. STIRPE and E. DELLA CORTE, The regulation of rat liver xanthine oxidase, J. Biol. Chem. 244, 3855-3863 (1969).
67. W. H. HABIG, M. J. PABST and W. B. JAKOBY, Glutathione S-transferases, J. Biol. Chem. 249, 7130-7139 (1974).
68. P. K. SMITH, R. I. KROHN, G. T. HERMANSON, A. K. MALLIA, F. H. GARTNER, M. D. PROVENZANO, E. K. FUJIMOTO, N. M. GOEKE, B. J. OLSON and D. C. KLENK, Measurement of protein using bicinchoninic acid, Anal. Biochem. 150, 76-85 (1985).
69. S. ROCKWELL, In vivo-in vitro tumor systems: new models for studying the response of tumors to therapy, Lab. Anim. Sci. 27, 831-851 (1977).
70. P. M. FRACASSO and A. C. SARTORELLI, Cytotoxicity and DNA lesions produced by mitomycin C and porfiromycin in hypoxic and aerobic EMT6 and Chinese hamster ovary cells, Cancer Res. 46, 3939-3944 (1986).
71. B. H. XU, V. GUPTA and S. V. SINGH, Mitomycin C sensitivity in human bladder cancer cells: possible role of glutathione and glutathione transferase in resistance, Arch. Biochem. Biophys. 308, 164-170 (1994).
72. B. KALYANARAMAN, E. PEREZ-REYES and R. P. MASON, Spin-trapping and direct electron spin resonance investigations of the redox metabolism of quinone anti-cancer drugs, Biochim. Biophys. Acta 630, 119-130 (1980).
73. L. DUSRE, S. RAJAGOPALAN, H. M. ELIOT, J. M. COVEY and B. K. SINHA, DNA interstrand cross-link and free radical formation in a human multidrug-resistant cell line from mitomycin C and its analogues, Cancer Res. 50, 648-652 (1990).
74. T. IYANAGI and I. YAMAZAKI, One-electron transfer reactions in biochemical systems III. One-electron reduction of quinones by microsomal flavin enzymes, Biochim. Biophys. Acta 172, 370-381 (1969).
75. R. T. DORR, G. T. BOWDEN, D. S. ALBERTS and J. D. LIDDIL, Interaction of mitomycin C with mammalian DNA detected by alkaline elution, Cancer Res. 45, 3510-3516 (1985).
76. H. D. BEALL, R. T. MULCAHY, D. SIEGEL, R. D. TRAVER, N. W. GIBSON and D. ROSS, Metabolism of bioreductive antitumor compounds by purified rat and human DT-diaphorases, Cancer Res. 54, 3196-3201 (1994).
77. A. BEGLEITER, M. K. LEITH, G. MCCLARTY, S. BEENKEN, G. J. GOLDENBERG and J. A. WRIGHT, Characterization of L5178Y murine lymphoblasts resistant to quinone antitumor agents, Cancer Res. 48, 1727-1735 (1988).
78. A. M. DULHANTY and G. F. WHITMORE, Chinese hamster ovary cell lines resistant to mitomycin C under aerobic but not hypoxic conditions are deficient in DT-diaphorase, Cancer Res. 51, 1860-1865 (1991).
79. C. CERA, M. EGBERTSON, S. P. TENG, D. M. CROTHERS and S. J. DANISHEFSKY, DNA cross-linking by intermediates in the mitomycin activation cascade, Biochemistry 28, 5665-5669 (1989).
80. R. S. MARSHALL and A. M. RAUTH, Oxygen and exposure kinetics as factors influencing the cytotoxicity of porfiromycin, a mitomycin C analogue, in Chinese hamster ovary cells, Cancer Res. 48, 5655-5659 (1988).
81. D. ROSS, H. D. BEALL, D. SIEGEL, R. D. TRAVER and D. L. GUSTAFSON, Enzymology of bioreductive drug activation, Brit. J. Cancer 74 (Suppl. 27), S1-S8 (1996).
82. N. ROBERTSON, I. J. STRATFORD, S. HOULBROOK, J. CARMICHAEL and G. E. ADAMS, The sensitivity of human tumor cells to quinone bioreductive drugs: what role for DT-diaphorase?, Biochem. Pharmacol. 44, 409-412 (1992).
83. S. R. KEYES, S. ROCKWELL and A. C. SARTORELLI, Modification of the metabolism and cytotoxicity of bioreductive alkylating agents by dicoumarol in aerobic and hypoxic murine tumor cells, Cancer Res. 49, 3310-3313 (1989).
84. S. R. KEYES, S. ROCKWELL and A. C. SARTORELLI, Enhancement of mitomycin C cytotoxicity to hypoxic tumor cells by dicoumarol in vivo and in vitro, Cancer Res. 45, 213-216 (1985).
85. S. ROCKWELL, S. R. KEYES and A. C. SARTORELLI, Modulation of the cytotoxicity of mitomycin C to EMT6 mouse mammary tumor cells by dicoumarol in vitro, Cancer Res. 48, 5471-5474 (1988).
86. S. ROCKWELL, S. R. KEYES and A. C. SARTORELLI, Modulation of the cytotoxicity of porfiromycin by dicoumarol in vitro and in vivo, Anticancer Res. 9, 817-820 (1989).
87. R. S. MARSHALL, M. C. PATERSON and A. M. RAUTH, Deficient activation by a human cell strain leads to mitomycin resistance under aerobic but not hypoxic conditions, Brit. J. Cancer 59, 341-346 (1989).
88. R. S. MARSHALL, M. C. PATERSON and A. M. RAUTH, Studies on the mechanism of resistance to mitomycin C and porfiromycin in a human cell strain derived from a cancer-prone individual, Biochem. Pharmacol. 41, 1351-1360 (1991).
89. D. H. MURRAY, J. MENDEZ and S. A. BROWN, Biological actions of 4-hydroxy-coumarins. in The Natural Coumarins: Occurrence, Chemistry, and Biochemistry. (R. D. H. MURRAY, J. MENDEZ and S. A. BROWN, eds.). Wiley-Interscience, New York, NY. Chap. 11 (1982).
90. 5 reductase (FpD) produces different sensitivities to the mitomycins in Chinese hamster ovary (CHO) cells, Proc. Am. Assoc. Cancer Res. 38, 1 (1997).
91. G. POWIS, P. Y. GASDASKA, A. GALLEGOS, K. SHERRILL and D. GOODMAN, Over-expression of DT-diaphorase in transfected NIH 3T3 cells does not lead to increased anticancer quinone drug sensitivity: a questionable role for the enzyme as a target for bioreductively activated anticancer drugs, Anticancer Res. 15, 1141-1146 (1995).
92. D. L. GUSTAFSON, H. D. BEALL, E. M. BOLTON, D. ROSS and C. A. WALDREN, Expression of human NAD(P)H:quinone oxidoreductase (DT-diaphorase) in Chinese hamster ovary cells: effect on the toxicity of antitumor quinones, Mol. Pharmacol. 50, 728-735 (1996).
93. K. MIKAMI, M. NAITO, A. TOMIDA, M. YAMADA, T. SIRAKUSA and T. TSURUO, DT-diaphorase as a critical determinant of sensitivity to mitomycin C in human colon and gastric carcinoma cell lines, Cancer Res. 56, 2823-2826 (1996).
94. T. YOSHIDA and H. TSUDA, Gene targeting of DT-diaphorase in mouse embryonic stem cells: establishment of null mutant and its mitomycin C-resistance, Biochem. Biophys. Res. Commun. 214, 701-708 (1995).
95. H. D. BEALL, A. M. MURPHY, D. SIEGEL, R. H. J. HARGREAVES, J. BUTLER and D. ROSS, Nicotinamide adenine dinucleotide (phosphate):quinone oxidoreductase (DT-diaphorase) as a target for bioreductive antitumor quinones: quinone cytotoxicity and selectivity in human lung and breast cancer cell lines, Mol. Pharmacol. 48, 499-504 (1995).
96. S. CHEN, R. KNOX, K. WU, P. S-K. DENG, D. ZHOU, M. A. BIANCHET and L. M. AMZEL, Molecular basis of the catalytic differences among DT-diaphorase of human, rat, and mouse, J. Biol. Chem. 272, 1437-1439 (1997).