Enzyme-Catalyzed Activation of Anticancer Prodrugs

Pharmacological Reviews

Volumn 56, Issue 1, 2004, Pages 53-102

  Rooseboom, Martijn ^a   Commandeur, Jan N M ^a   Vermeulen, Nico P E ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 BIS[[2 (DIMETHYLAMINO N OXIDE)ETHYL]AMINO] 5,8 DIHYDROXYANTHRAQUINONE; 2 (3 AMINOPROPYLAMINO)ETHANETHIOL; 5 (1 AZIRIDINYL) 2,4 DINITROBENZAMIDE; 5 (1 AZIRIDINYL) 3 HYDROXYMETHYL 2 (3 HYDROXY 1 PROPENYL) 1 METHYL 4,7 INDOLEDIONE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; ALDEHYDE OXIDASE; ALKALINE PHOSPHATASE; AMIFOSTINE; AMINO ACID OXIDASE; ANTINEOPLASTIC AGENT; BETA GLUCURONIDASE; BETA LACTAMASE; BMY 46633; CANFOSFAMIDE; CARBOXYLESTERASE; CYSTEINE CONJUGATE BETA LYASE; CYTOCHROME P450; CYTOCHROME P450 REDUCTASE; CYTOSINE DEAMINASE; DEOXYCYTIDINE KINASE; DOXORUBICIN; FLUCYTOSINE; FLUOROURACIL; GANCICLOVIR; GLUTATHIONE TRANSFERASE; IFOSFAMIDE; IRINOTECAN; LY 266070; METHIONINE GAMMA LYASE; MONOPHENOL MONOOXYGENASE; N (4 BETA GLUCURONYL 3 NITROBENZYLOXYCARBONYL)DOXORUBICIN; NB 1011; PACLITAXEL; PENICILLIN AMIDASE; PRODRUG; PURINE NUCLEOSIDE PHOSPHORYLASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); THYMIDINE PHOSPHORYLASE; THYMIDYLATE SYNTHASE; TIRAPAZAMINE; TROFOSFAMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BONE MARROW SUPPRESSION; CANCER PREVENTION; CARDIOTOXICITY; DEAMINATION; DNA ALKYLATION; DNA SYNTHESIS INHIBITION; DRUG ACTIVATION; DRUG BIOAVAILABILITY; DRUG CONJUGATION; DRUG SELECTIVITY; DRUG TARGETING; ENZYME INHIBITION; ENZYME LOCALIZATION; ENZYME SUBSTRATE COMPLEX; GASTROINTESTINAL SYMPTOM; GENE THERAPY; HUMAN; MICROTUBULE; NAUSEA; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; RADIOSENSITIZATION; REVIEW; TISSUE DISTRIBUTION; VOMITING;

ANIMALS; ANTINEOPLASTIC AGENTS; CATALYSIS; ENZYME ACTIVATION; HUMANS; NEOPLASMS; PRODRUGS;

EID: 1542376883     PISSN: 00316997     EISSN: None     Source Type: Journal    
DOI: 10.1124/pr.56.1.3     Document Type: Review

References (220)

1. Aghi M, Hochberg F, and Breakefield XO (2000) Prodrug activation enzymes in cancer gene therapy. J Gene Med 2:148-164.
2. Albert A (1958) Chemical aspects of selective toxicity. Nature (Lond) 182:421-423.
3. Aldridge WN (1953) Serum esterases: two types of esterases (A and B) hydrolyzing para-nitrophenylacetate, propionate and a method for their determination. Biochem J 53:110-119.
4. Andreadou I, Menge WMPB, Commandeur JNM, Worthington EA, and Vermeulen NPE (1996) Synthesis of novel Se-substituted selenocysteine derivatives as potential kidney selective prodrugs of biologically active selenol compounds: evaluation of kinetics of β-elimination reactions in rat renal cytosol. J Med Chem 39:2040-2046.
5. Anlezark GM, Melton RG, Sherwood RF, Coles B, Friedlos F, and Knox RJ (1992) The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)-I. Purification and properties of a nitroreductase enzyme from Escherichia coli-a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT). Biochem Pharmacol 44:2289-2295.
6. Armstrong RD and Diasio RB (1980) Metabolism and biological activity of 5′-deoxy-5-fluorouridine, a novel fluoropyrimidine. Cancer Res 40:3333-3338.
7. Arner ES and Eriksson S (1995) Mammalian deoxyribonucleoside kinases. Pharmacol Ther 67:155-186.
8. Arner ES, Spasokoukotskaja T, and Eriksson S (1992) Selective assays for thymidine kinase 1 and 2 and deoxycytidine kinase and their activities in extracts from human cells and tissues. Biochem Biophys Res Commun 188:712-718.
9. Au JL and Sadee W (1981) The pharmacology of ftorafur (R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil. Recent Res Cancer Res 76:100-114.
10. Bachur NR, Gordon SL, Gee MV, and Kon H (1979) NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals. Proc Natl Acad Sci USA 76:954-957.
11. Bagshawe KD and Begent RHJ (1996) First clinical experience with ADEPT. Adv Drug Delivery Rev 22:365-367.
12. Bailey SM, Lewis AD, Patterson LH, Fisher GR, Knox RJ, and Workman P (2001) Involvement of NADPH: cytochrome P450 reductase in the activation of indoloquinone EO9 to free radical and DNA damaging species. Biochem Pharmacol 62:461-468.
13. Bakina E, Wu Z, Rosenblum M, and Farquhar D (1997) Intensely cytotoxic anthracycline prodrugs: glucuronides. J Med Chem 40:4013-4018.
14. Barker RF and Hopkinson DA (1977) The genetic and biochemical properties of the D-amino acid oxidases in human tissues. Ann Hum Genet 41:27-42.
15. Baron J, Kawabata TT, Redick JA, Knapp SA, Wick DG, Wallace RB, Jacoby WB, and Guengerich FP (1983) Localization of carcinogen-metabolizing enzymes in human and animal tissue, in Extrahepatic Metabolism and Chemical Carcinogenesis (Rydstrom J, Montelius J and Bengtsson M eds) pp 73-88, Elsevier, Amsterdam.
16. Bathe OF, Franceschi D, Livingstone AS, Moffat FL, Tian E, and Ardalan B (1999) Increased thymidylate synthase gene expression in liver metastases from colorectal carcinoma: implications for chemotherapeutic options and survival. Cancer J Sci Am 5:34-40.
17. Beall HD, Liu Y, Siegel D, Bolton EM, Gibson NW, 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.
18. Beedham C, Bruce SE, and Rance DJ (1987) Tissue distribution of the molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase, in male and female guinea pigs. Eur J Drug Metab Pharmacokinet 12:303-306.
19. Begleiter A (2000) Clinical applications of quinone-containing alkylating agents. Front Biosci 5:E153-E171.
20. Belcourt MF, Hodnick WF, Rockwell S, and Sartorelli AC (1998) Exploring the mechanistic aspects of mitomycin antibiotic bioactivation in Chinese hamster ovary cells overexpressing NADPH: cytochrome C (P-450) reductase and DT-diaphorase. Adv Enzyme Regul 38:111-133.
21. Benedetto C, Slater TF, and Dianzani MU (1976) NADPH-cytochrome c reductase, cytochrome P-450 and NADPH-linked lipid peroxidation in microsomal fractions obtained from rat tissue. Biochem Soc Trans 4:1094-1097.
22. Bignami GS, Senter PD, Grothaus PG, Fischer KJ, Humphreys T, and Wallace PM (1992) N-(4′-Hydroxyphenylacetyl)palytoxin: a palytoxin prodrug that can be activated by a monoclonal antibody-penicillin G amidase conjugate. Cancer Res 52:5759-5764.
23. Blakey DC, Valcaccia BE, East S, Wright AF, Boyle FT, Springer CJ, Burke PJ, Melton RG, and Bagshawe KD (1993) Antitumor effects of an antibody-carboxypeptidase G2 conjugate in combination with a benzoic acid mustard prodrug. Cell Biophys 22:1-8.
24. Boddy AV and Yule SM (2000) Metabolism and pharmacokinetics of oxazaphosphorines. Clin Pharmacokinet 38:291-304.
25. Boland MP, Knox RJ, and Roberts JJ (1991) 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-yl)-2,4-dinitrobenzamide). Biochem Pharmacol 41:867-875.
26. Bolzan AD and Bianchi MS (2001) Genotoxicity of streptonigrin: a review. Mutat Res 488:25-37.
27. Bosslet K, Czech J, and Hoffmann D (1994) Tumor-selective prodrug activation by fusion protein-mediated catalysis. Cancer Res 54:2151-2159.
28. Boyd MR (1977) Evidence for the Clara cell as a site of cytochrome P450-dependent mixed-function oxidase activity in lung. Nature (Lond) 269:713-715.
29. Boyd MR and Wilson BJ (1972) Isolation and characterization of 4-ipomeanol, a lung-toxic furanoterpenoid produced by sweet potatoes (Ipomoea batatas). J Agric Food Chem 20:428-430.
30. Brown JM (1993) SR 4233 (tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours. Br J Cancer 67:1163-1170.
31. Brown NS and Bicknell R (1998) Thymidine phosphorylase, 2-deoxy-D-ribose and angiogenesis. Biochem J 334:1-8.
32. Budman DR (2000) Capecitabine. Investig New Drugs 18:355-363.
33. Buetler TM, Gallagher EP, Wang C, Stahl DL, Hayes JD, and Eaton DL (1995) Induction of phase I and phase II drug-metabolizing enzyme mRNA, protein, and activity by BHA, ethoxyquin and oltipraz. Toxicol Appl Pharmacol 135:45-57.
34. Bzowska A, Kulikowska E, and Shugar D (2000) Purine nucleoside phosphorylases: properties, functions and clinical aspects. Pharmacol Ther 88:349-425.
35. Calabro-Jones PM, Fahey RC, Smoluk GD, and Ward JF (1985) Alkaline phosphatase promotes radioprotection and accumulation of WR-1065 in V79-171 cells incubated in medium containing WR-2721. Int J Radiat Biol Relat Stud Phys Chem Med 47:23-27.
36. Carreras CW and Santi DV (1995) The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem 64:721-762.
37. Chan TS, Lakhchaura BD, and Hsu TF (1983) Differences in deoxycytidine metabolism in mouse and rat. Biochem J 210:367-371.
38. Chen S, Knox R, Wu K, Deng PS, Zhou D, Bianchet MA, and Amzel LM (1997) Molecular basis of the catalytic differences among DT-diaphorase of human, rat and mouse. J Biol Chem 272:1437-1439.
39. Chinje EC, Patterson AV, Saunders MP, Lockyer SD, Harris AL, and Stratford IJ (1999) Does reductive metabolism predict response to tirapazamine (SR 4233) in human non-small-cell lung cancer cell lines? Br J Cancer 81:1127-1133.
40. Choong YS, Lee SP, and Alley PA (1988) Comparison of the pyrimidine nucleoside phosphorylase activity in human tumors and normal tissues. Exp Pathol 33:23-25.
41. Cole C, Foster AJ, Freeman S, Jaffar M, Murray PE, and Strafford IJ (1999) The role of thymidine phosphorylase/PD-ECGF in cancer chemotherapy: a chemical perspective. Anticancer Drug Des 14:383-392.
42. Collie-Duguid ES, Johnston SJ, Boyce L, Smith N, Cowieson A, Cassidy J, Murray GI, and McLeod HL (2001) Thymidine phosphorylase and dihydropyrimidine dehydrogenase protein expression in colorectal cancer. Int J Cancer 94:297-301.
43. Commandeur JNM, Andreadou I, Rooseboom M, Out M, de Leur LJ, Groot E, and Vermeulen NPE (2000) Bioactivation of selenocysteine Se-conjugates by a highly purified rat renal cysteine conjugate beta-lyase/glutamine transaminase K. J Pharmacol Exp Ther 294:753-761.
44. Commandeur JNM, Stijntjes GJ, and Vermeulen NPE (1995) Enzymes and transport systems involved in the formation and disposition of glutathione S-conjugates. Role in bioactivation and detoxication mechanisms of xenobiotics. Pharmacol Rev 47:271-330.
45. Connors TA (1986) Prodrugs in cancer chemotherapy. Xenobiotica 16:975-988.
46. Coombs GH and Mottram JC (2001) Trifluoromethionine, a prodrug designed against methionine gamma-lyase-containing pathogens, has efficacy in vitro and in vivo against Trichomonas vaginalis. Antimicrob Agents Chemother 45:1743-1745.
47. Cooper AJL (1998) Mechanisms of cysteine S-conjugate beta-lyases. Adv Enzymol 72:199-237.
48. Crystal RG (1999) In vivo and ex vivo gene therapy strategies to treat tumors using adenovirus gene transfer vectors. Cancer Chemother Pharmacol 43:S90-S99.
49. Cummings J, Spanswick VJ, and Smyth JF (1995) Re-evaluation of the molecular pharmacology of mitomycin C. Eur J Cancer 31A:1928-1933.
50. Cummings J, Spanswick VJ, Tomasz M, and Smyth JF (1998) Enzymology of mitomycin C metabolic activation in tumour tissue: implications for enzyme-directed bioreductive drug development. Biochem Pharmacol 56:405-414.
51. Cunningham C and Nemunaitis J (2001) A phase I trial of genetically modified Salmonella typhimurium expressing cytosine deaminase (TAPET-CD, VNP20029) administered by intratumoral injection in combination with 5-fluorocytosine for patients with advanced or metastatic cancer. Protocol no: CL-017. Version: April 9, 2001. Hum Gene Ther 12:1594-1596.
52. Curti B, Rorchi S, and Simonetta MP (1992) D- and L-amino acid oxidases, in Chemistry and Biochemistry of Flavoenzymes (Müller F ed) pp 69-94, CRC Press, Boca Raton, FL.
53. Czerwinski M, McLemore TL, Philpot RM, Nhamburo PT, Korzekwa K, Gelboin HV, and Gonzalez FJ (1991) Metabolic activation of 4-ipomeanol by complementary DNA-expressed human cytochromes P-450: evidence for species-specific metabolism. Cancer Res 51:4636-4638.
54. Danenberg PV, Malli H, and Swenson S (1999) Thymidylate synthase inhibitors. Semin Oncol 26:621-631.
55. de Bont DB, Leenders RG, Haisma HJ, van der Meulen-Muileman I, and Scheeren HW (1997) Synthesis and biological activity of beta-glucuronyl carbamate-based prodrugs of paclitaxel as potential candidates for ADEPT. Bioorg Med Chem 5:405-414.
56. Della Morte R, Belisario MA, Remondelli P, Mugnoz B, and Staiano N (1986) In vitro activation of isophosphamide and trophosphamide to metabolites mutagenic for bacteria. Toxicol Lett 31:183-188.
57. del Marmol V and Beermann F (1996) Tyrosinase and related proteins in maromalian pigmentation. FEBS Lett 381:165-168.
58. Denny WA and Wilson WR (2000) Tirapazamine: a bioreductive anticancer drug that exploits tumour hypoxia. Expert Opin Investig Drugs 9:2889-2901.
59. Deonarain MP and Epenetos AA (1994) Targeting enzymes for cancer therapy: old enzymes in new roles. Br J Cancer 70:786-794.
60. Deonarain MP, Spooner RA, and Epenetos AA (1995) Genetic delivery of enzymes for cancer therapy. Gene Ther 2:235-244.
61. DePierre JW and Morgenstern R (1983) Comparison of the distribution of microsomal and cytosolic glutathione S-transferase activities in different organs of the rat. Biochem Pharmacol 32:721-723.
62. Desbene S, Van HD, Michel S, Koch M, Tillequin F, Fournier G, Farjaudon N, and Monneret C (1998) Doxorubicin prodrugs with reduced cytotoxicity suited for tumour-specific activation. Anticancer Drug Des 13:955-968.
63. Dewey DL, Butcher FW, and Galpine AR (1977) Hydroxyanisole-induced regression of the Harding-Passey melanoma in mice. J Pathol 122:117-127.
64. Dollery C (1991) Dacarbazine, in Therapeutic Drugs (Dollery C ed) pp D1-D3, Churchill Livingstone, London, UK.
65. Dubowchik GM and Walker MA (1999) Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs. Pharmacol Ther 83:67-123.
66. Eda H, Fujimoto K, Watanabe S, Ura M, Hino A, Tanaka Y, Wada K, and Ishitsuka H (1993) Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5′-deoxy-5-fluorouridine. Cancer Chemother Pharmacol 32:333-338.
67. Elfarra AA, Duescher RJ, Hwang IY, Sicuri AR, and Nelson JA (1995) Targeting 6-thioguanine to the kidney with S-(guanin-6-yl)-L-cysteine. J Pharmacol Exp Ther 274:1298-1304.
68. Esaki N and Soda K (1987) L-methionine gamma-lyase from Pseudomonas putida and Aeromonas. Methods Enzymol 143:459-465.
69. Esaki N, Tanaka H, Uemura S, Suzuki T, and Soda K (1979) Catalytic action of L-methionine gamma-lyase on selenomethionine and selenols. Biochemistry 18:407-410.
70. Estenius M, Forsberg L, Danielsson O, Weinander R, Kelner MJ, and Morgenstern R (1999) Distribution of microsomal glutathione transferase 1 in mammalian tissues. A predominant alternate first exon in human tissues. Eur J Biochem 260:409-413.
71. Evrard A, Cuq P, Ciccolini J, Vian L, and Cano JP (1999) Increased cytotoxicity and bystander effect of 5-fluorouracil and 5-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase. Br J Cancer 80:1726-1733.
72. Fisher GR and Gutierrez PL (1991) 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 11:597-607.
73. Fishman WH (1995) The 1993 ISOBM Abbott Award Lecture. Isozymes, tumor markers and oncodevelopmental biology. Tumour Biol 16:394-402.
74. Florent JC, Dong X, Gaudel G, Mitaku S, Monneret C, Gesson JP, Jacquesy JC, Mondon M, Renoux B, Andrianomenjanahary S, et al. (1998) Prodrugs of anthracyclines for use in antibody-directed enzyme prodrug therapy. J Med Chem 41:3572-3581.
75. Forkert PG, Lord JA, and Parkinson A (1996) Alterations in expression of CYP1A1 and NADPH-cytochrome P450 reductase during lung tumor development in SWR/J mice. Carcinogenesis 17:127-132.
76. Friery OP, Gallagher R, Murray MM, Hughes CM, Galligan ES, McIntyre IA, Patterson LH, Hirst DG, and McKeown SR (2000) Enhancement of the antitumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. Br J Cancer 82:1469-1473.
77. Gadi VK, Alexander SD, Kudlow JE, Allan P, Parker WB, and Sorscher EJ (2000) In vivo sensitization of ovarian tumors to chemotherapy by expression of E. coli purine nucleoside phosphorylase in a small fraction of cells. Gene Ther 7:1738-1743.
78. Gallagher R, Hughes CM, Murray MM, Friery OP, Patterson LH, Hirst DG, and McKeown SR (2001) The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N. Br J Cancer 85:625-629.
79. Gili A, Thomas PD, Ota M, and Jimbow K (2000) Comparison of in vitro cytotoxicity of N-acetyl and N-propionyl derivatives of phenolic thioether amines in melanoma and neuroblastoma cells and the relationship to tyrosinase and tyrosine hydroxylase enzyme activity. Melanoma Res 10:9-15.
80. Gram TE (1997) Chemically reactive intermediates and pulmonary xenobiotic toxicity. Pharmacol Rev 49:297-341.
81. Greco O and Dachs GU (2001) Gene directed enzyme/prodrug therapy of cancer: historical appraisal and future prospectives. J Cell Physiol 187:22-36.
82. Griffiths L and Stratford IJ (1997) Platelet-derived endothelial cell growth factor thymidine phosphorylase in tumour growth and response to therapy. Br J Cancer 76:689-693.
83. Grove JI, Searle PF, Weedon SJ, Green NK, McNeish IA, and Kerr DJ (1999) Virus-directed enzyme prodrug therapy using CB1954. Anticancer Drug Des 14:461-472.
84. Guerquin-Kern JL, Volk A, Chenu E, Lougerstay-Madec R, Monneret C, Florent JC, Carrez D, and Croisy A (2000) Direct in vivo observation of 5-fluorouracil release from a prodrug in human tumors heterotransplanted in nude mice: a magnetic resonance study. NMR Biomed 13:306-310.
85. Gunnarsdottir S and Elfarra AA (1999) Glutathione-dependent metabolism of cis-3-(9H-purin-6-ylthio)acrylic acid to yield the chemotherapeutic drug 6-mercaptopurine: evidence for two distinct mechanisms in rats. J Pharmacol Exp Ther 290:950-957.
86. Guo X, Lerner-Tung M, Chen HX, Chang CN, Zhu JL, Chang CP, Pizzorno G, Lin TS, and Cheng YC (1995) 5-Fluoro-2-pyrimidinone, a liver aldehyde oxidase-activated prodrug of 5-fluorouracil. Biochem Pharmacol 49:1111-1116.
87. Haffty BG, Son YH, Sasaki CT, Papac R, Fischer D, Rockwell S, Sartorelli A, and Fischer JJ (1993) 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.
88. Haisma HJ, Boven E, van Muijen M, de Jong J, van der Vijgh WJ, and Pinedo HM (1992) A monoclonal antibody-beta-glucuronidase conjugate as activator of the prodrug epirubicin-glucuronide for specific treatment of cancer. Br J Cancer 66:474-478.
89. Haisma HJ, van Muijen M, Pinedo HM, and Boven E (1994) Comparison of two anthracycline-based prodrugs for activation by a monoclonal antibody-beta-glucuronidase conjugate in the specific treatment of cancer. Cell Biophys 25:185-192.
90. Hall PM, Stupans I, Burgess W, Birkett DJ, and McManus ME (1989) Immunohistochemical localization of NADPH-cytochrome P450 reductase in human tissues. Carcinogenesis 10:521-530.
91. Hamilton DS, Kavarana MJ, Sharkey EM, Eiseman JL, and Creighton DJ (1999) A new method for rapidly generating inhibitors of glyoxalase I inside tumor cells using S-(N-aryl-N-hydroxycarbamoyl)ethylsulfoxides. J Med Chem 42:1823-1827.
92. Hamilton GA (1985) Peroxisomal oxidases and suggestions for the mechanism of action of insulin and other hormones. Adv Enzymol Relat Areas Mol Biol 57:85-178.
93. Hande KR (1998) Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer 34:1514-1521.
94. Hanessian S and Wang J (1993) Design and synthesis of a cephalosporin-carboplatinum prodrug activatable by a β-lactamase. Can J Chem 71:896-906.
95. Hapke DM, Stegmann AP, and Mitchell BS (1996) Retroviral transfer of deoxycytidine kinase into tumor cell lines enhances nucleoside toxicity. Cancer Res 56:2343-2347.
96. Hargreaves RH, Hartley JA, and Butler J (2000) Mechanisms of action of quinone-containing alkylating agents: DNA alkylation by aziridinylquinones. Front Biosci 5:E172-E180.
97. Harkrader RJ, Jackson RC, Ross DA, and Weber G (1980) Increase in liver and kidney deoxycytidine kinase activity linked to neoplastic transformation. Biochem Biophys Res Commun 96:1633-1639.
98. Harvey WK and Lindahl R (1982) Activity of various aldehyde-metabolizing enzymes in chemically-induced rat hepatomas. Biochem Pharmacol 31:1153-1155.
99. Hasegawa K, Ito S, Inoue S, Wakamatsu K, Ozeki H, and Ishiguro I (1997) Dihydro-1,4-benzothiazine-6,7-dione, the ultimate toxic metabolite of 4-S-cysteaminylphenol and 4-S-cysteaminylcatechol. Biochem Pharmacol 53:1435-1444.
100. Hashimoto Y, Shiotani T, Eble JN, Glover JL, and Weber G (1988) Increased thymidylate synthase (EC 2.1.1.45) activity in normal and neoplastic proliferation. Cancer Biochem Biophys 10:1-10.
101. Hata Y, Takahashi H, Sasaki F, Ogita M, Uchino J, Yoshimoto M, Akasaka Y, Nakanishi Y, and Sawada Y (2000) Intratumoral pyrimidine nucleoside phosphorylase (PyNPase) activity predicts a selective effect of adjuvant 5′-deoxy-5-fluorouridine (5′DFUR) on breast cancer. Breast Cancer 7:37-41.
102. Hayes JD and Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30:445-600.
103. Herzfeld A and Raper SM (1980) Relative activities of thymidylate synthetase and thymidine kinase in rat tissues. Cancer Res 40:744-750
104. Holmberg JT, Hultberg B, Hagerstrand I, Ihse I, and Isaksson A (1986) Tissue content and localization of lysosomal enzymes in cholestatic rats. Scand J Gastroenterol 21:205-214.
105. Holme DJ and Goldberg DM (1982) Development of a fluorometric assay for aminoacid oxidase activity and its application to the study of human tissues. Biochem Med 28:51-61.
106. Houba PH, Boven E, van der Meulen-Muileman IH, Leenders RG, Scheeren JW, Pinedo HM, and Haisma HJ (1999) Distribution and pharmacokinetics of the prodrug daunorubicin-GA3 in nude mice bearing human ovarian cancer xenografts. Biochem Pharmacol 57:673-680.
107. Houba PH, Boven E, van der Meulen-Muileman IH, Leenders RG, Scheeren JW, Pinedo HM, and Haisma HJ (2001a) A novel doxorubicin-glucuronide prodrug DOX-GA3 for tumour-selective chemotherapy: distribution and efficacy in experimental human ovarian cancer. Br J Cancer 84:550-557.
108. Houba PH, Boven E, van der Meulen-Muileman IH, Leenders RG, Scheeren JW, Pinedo HM, and Haisma HJ (2001b) Pronounced antitumor efficacy of doxorubicin when given as the prodrug DOX-GA3 in combination with a monoclonal antibody beta-glucuronidase conjugate. Int J Cancer 91:550-554.
109. Houba PH, Leenders RG, Boven E, Scheeren JW, Pinedo HM, and Haisma HJ (1996) Characterization of novel anthracycline prodrugs activated by human beta-glucuronidase for use in antibody-directed enzyme prodrug therapy. Biochem Pharmacol 52:455-463.
110. Huang P and Plunkett W (1987) Phosphorolytic cleavage of 2-fluoroadenine from 9-beta-D-arabinofuranosyl-2-fluoroadenine by Escherichia coli. A pathway for 2-fluoro-ATP production. Biochem Pharmacol 36:2945-2950.
111. Huang PS and Oliff A (2001) Drug-targeting strategies in cancer therapy. Curr Opin Genet Dev 11:104-110.
112. Huang Z, Roy P, and Waxman DJ (2000) Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzing N-dechloroethylation of cyclophosphamide and ifosfamide. Biochem Pharmacol 59:961-972.
113. Hudyma TW, Bush K, Colson KL, Firestone RA, and King HD (1993) Synthesis and release of doxorubicin from a cephalosporin based prodrug by a β-lactamase-immunoconjugate. Bioorg Med Chem Lett 3:323-328.
114. Philpott GW, Shearer WT, Bower RJ, and Parker CW (1973) Selective cytotoxicity of hapten-substituted cells with an antibody-enzyme conjugate. J Immunol 111:921-929.
115. Plewka D, Plewka A, Nowaczyk G, Kaminski M, Rutkowski T, Ludyga T, and Ziaja K (2000) Neoplastic lesions of the human liver in relation to the activity of the cytochrome P-450 dependent monooxygenase system. Med Sci Monit 6:244-248.
116. Porter DJ, Harrington JA, Almond MR, Lowen GT, Zimmerman TP, and Spector T (1994) 5-Ethynyl-2(1H)-pyrimidinone: aldehyde oxidase-activation to 5-ethynyluracil, a mechanism-based inactivator of dihydropyrimidine dehydrogenase. Biochem Pharmacol 47:1165-1171.
117. Powis G, Gasdaska PY, Gallegos A, Sherrill K, and Goodman D (1995) Overexpression 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 15:1141-1145.
118. Preiss R, Schmidt R, Baumann F, Hanschmann H, Hauss J, Geissler F, Pahlig H, and Ratzewiss B (2002) Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol 128:385-392.
119. Prezioso JA, Damodaran KM, Wang N, and Bloomer WD (1993) Mechanism(s) regulating inhibition of thymidylate synthase and growth by gamma-L-glutaminyl-4-hydroxy-3-iodobenzene, a novel melanin precursor, in melanogenic melanoma cells. Biochem Pharmacol 45:473-481.
120. Prezioso JA, Epperly MW, Wang N, and Bloomer WD (1992a) Effects of tyrosinase activity on the cytotoxicity of 4-S-cysteaminylphenol and N-acetyl-4-S-cysteaminylphenol in melanoma cells. Cancer Lett 63:73-79.
121. Prezioso JA, Hughey RP, Wang N, Damodaran KM, and Bloomer WD (1994) Gamma-glutamyltranspeptidase expression regulates the growth-inhibitory activity of the antitumor prodrug gamma-L-glutaminyl-4-hydroxy-3-iodobenzene. Int J Cancer 56:874-879.
122. Prezioso JA, Wang N, and Bloomer WD (1992b) Thymidylate synthase as a target enzyme for the melanoma-specific toxicity of 4-S-cysteaminylphenol and N-acetyl-4-S-cysteaminylphenol. Cancer Chemother Pharmacol 30:394-400.
123. Punt CJ (1998) New drugs in the treatment of colorectal carcinoma. Cancer 83:679-689.
124. Raleigh SM, Wanogho E, Burke MD, McKeown SR, and Patterson LH (1998) Involvement of human cytochromes P450 (CYP) in the reductive metabolism of AQ4N, a hypoxia activated anthraquinone di-N-oxide prodrug. Int J Radiat Oncol Biol Phys 42:763-767.
125. Raleigh SM, Wanogho E, Burke MD, and Patterson LH (1999) Rat cytochromes P450 (CYP) specifically contribute to the reductive bioactivation of AQ4N, an alkylami-noanthraquinone-di-N-oxide anticancer prodrug. Xenobiotica 29:1115-1122.
126. Rao KN and Noronha JM (1977) Studies on the enzymatic hydrolysis of polyglutamyl folates by chicken liver folyl poly-gamma-glutamyl carboxypeptidase. I. Intracellular localization, purification and partial characterization of the enzyme. Biochim Biophys Acta 481:594-607.
127. Reid JM, Kuffel MJ, Miller JK, Rios R, and Ames MM (1999) Metabolic activation of dacarbazine by human cytochromes P450: the role of CYPIA1, CYPIA2 and CYP2E1. Clin Cancer Res 5:2192-2197.
128. Riley PA, Cooksey CJ, Johnson CI, Land EJ, Latter AM, and Ramsden CA (1997) Melanogenesis-targeted anti-melanoma pro-drug development: effect of side-chain variations on the cytotoxicity of tyrosinase-generated ortho-quinones in a model screening system. Eur J Cancer 33:135-143.
129. Riley RJ and Workman P (1992) DT-diaphorase and cancer chemotherapy. Biochem Pharmacol 43:1657-1669.
130. Rivory LP (2000) Metabolism of CPT-11. Impact on activity. Ann NY Acad Sci 922:205-215.
131. Rockwell S and Sartorelli AC (1990) Mitomycin C and radiation, in Antitumor Drug-Radiation Interactions (Hill BT and Bellamy AS eds) pp 125-139, CRC Press Inc. Boca Raton, FL.
132. Rodrigues ML, Carter P, Wirth C, Mullins S, Lee A, and Blackburn BK (1995a) Synthesis and beta-lactamase-mediated activation of a cephalosporin-taxol prodrug. Chem Biol 2:223-227.
133. Rodrigues ML, Presta LG, Kotts CE, Wirth C, Mordenti J, Osaka G, Wong WL, Nujiens A, Blackburn B, and Carter P (1995b) Development of a humanized disulfide-stabilized anti-p185HER2 Fv-beta-lactamase fusion protein for activation of a cephalosporin doxorubicin prodrug. Cancer Res 55:63-70.
134. Rodriguez-Lopez JN, Banon-Arnao M, Martinez-Ortiz F, Tudela J, Acosta M, Varon R, and Garcia-Canovas F (1992) Catalytic oxidation of 2,4,5-trihydroxyphenylalanine by tyrosinase: identification and evolution of intermediates. Biochim Biophys Acta 1160:221-228.
135. Rodriquez GI, Valdivieso M, Von Hoff DD, Kraut M, Burris HA, Eckardt JR, Lockwood G, Kennedy H, and Von Roemeling R (1996) A phase I/II trial of the combination of tirapazamine and cisplatin in patients with non-small cell lung canter (NSCLC) (Meeting abstract). Proc Annu Meet Am Soc Clin Oncol 15:382.
136. Roffler SR, Wang SM, Chern JW, Yeh MY, and Tung E (1991) Anti-neoplastic glucuronide prodrug treatment of human tumor cells targeted with a monoclonal antibody-enzyme conjugate. Biochem Pharmacol 42:2062-2065.
137. Rooseboom M, Commandeur JNM, Floor GC, Rettie AE, and Vermeulen NPE (2001a) Selenoxidation by flavin-containing monooxygenases as a novel pathway for β-elimination of selenocysteine Se-conjugates. Chem Res Toxicol 14:127-134.
138. Rooseboom M, Vermeulen NPE, Andreadou I, and Commandeur JNM (2000) Evaluation of kinetics of β-elimination reactions of selenocysteine Se-conjugates in human renal cytosol. Possible implications for the use as kidney selective prodrugs. J Pharmacol Exp Ther 294:762-769.
139. Rooseboom M, Vermeulen NPE, Groot EJ, and Commandeur JNM (2002) Tissue distribution of cytosolic β-elimination reactions of selenocysteine Se-conjugates in rat and human. Chem Biol Interact 140:243-264.
140. Rooseboom M, Vermeulen NPE, van Hemert N, and Commandeur JNM (2001b) Bioactivation of chemopreventive selenocysteine Se-conjugates and related amino acids by amino acid oxidases. Novel route of metabolism of selenoamino acids. Chem Res Toxicol 14:996-1005.
141. Rosario LA, O'Brien ML, Henderson CJ, Wolf CR, and Tew KD (2000) Cellular response to a glutathione S-transferase P1-1 activated prodrug. Mol Pharmacol 58:167-174.
142. Ross D, Beall H, Traver RD, Siegel D, Phillips RM, and Gibson NW (1994) Bioactivation of quinones by DT-diaphorase, molecular, biochemical and chemical studies. Oncol Res 6:493-500.
143. Ross D, Beall HD, Siegel D, Traver RD, and Gustafson DL (1996) Enzymology of bioreductive drug activation. Br J Cancer Suppl 27:S1-S8.
144. Ross D, Siegel D, Gibson NW, Pacheco D, Thomas DJ, Reasor M, and Wierda D (1990) Activation and deactivation of quinones catalyzed by DT-diaphorase. Evidence for bioreductive activation of diaziquone (AZQ) in human tumor cells and detoxification of benzene metabolites in bone marrow stroma. Free Radic Res Commun 8:373-381.
145. Roy P, Yu LJ, Crespi CL, and Waxman DJ (1999) Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos 27:655-666.
146. Santini V (2001) Amifostine: chemotherapeutic and radiotherapeutic protective effects. Expert Opin Pharmacother 2:479-489.
147. Santini V and Giles FJ (1999) The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica 84:1035-1042.
148. Satoh T and Hosokawa M (1995) Molecular aspects of carboxylesterase isoforms in comparison with other esterases. Toxicol Lett 82-83:439-445.
149. Satoh T, Hosokawa M, Atsumi R, Suzuki W, Hakusui H, and Nagai E (1994) Metabolic activation of CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, a novel antitumor agent, by carboxylesterase. Biol Pharm Bull 17:662-664.
150. Satyam A, Hocker MD, Kane-Maguire KA, Morgan AS, Villar HO, and Lyttle MH (1996) Design, synthesis and evaluation of latent alkylating agents activated by glutathione S-transferase. J Med Chem 39:1736-1747.
151. Saunders MP, Jaffar M, Patterson AV, Nolan J, Naylor MA, Phillips RM, Harris AL, and Stratford IJ (2000a) The relative importance of NADPH: cytochrome c (P450) reductase for determining the sensitivity of human tumour cells to the indolequinone EO9 and related analogues lacking functionality at the C-2 and C-3 positions. Biochem Pharmacol 59:993-996.
152. Saunders MP, Patterson AV, Chinje EC, Harris AL, and Stratford IJ (2000b) NADPH: cytochrome c (P450) reductase activates tirapazamine (SR4233) to restore hypoxic and oxic cytotoxicity in an aerobic resistant derivative of the A549 lung cancer cell line. Br J Cancer 82:651-656.
153. Schally AV and Nagy A (1999) Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors. Eur J Endocrinol 141:1-14.
154. Schlager JJ 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.
155. Schmidt R, Baumann F, Hanschmann H, Geissler F, and Preiss R (2001) Gender difference in ifosfamide metabolism by human liver microsomes. Eur J Drug Metab Pharmacokinet 26:193-200.
156. Schomburg D and Stephan D (1990-1998) Enzyme Handbook, Springer-Verlag, Berlin, Germany.
157. Senter PD (1990) Activation of prodrugs by antibody-enzyme conjugates: a new approach to cancer therapy. FASEB J 4:188-193.
158. Senter PD, Marquardt H, Thomas BA, Hammock BD, Frank IS, and Svensson HP (1996) The role of rat serum carboxylesterase in the activation of paclitaxel and camptothecin prodrugs. Cancer Res 56:1471-1474.
159. Senter PD, Saulnier MG, Schreiber GJ, Hirschberg DL, Brown JP, Hellstrom I, and Hellstrom KE (1988) Antitumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate. Proc Natl Acad Sci USA 85:4842-4846.
160. Senter PD, Schreiber GJ, Hirschberg DL, Ashe SA, Hellstrom KE, and Hellstrom I (1989) Enhancement of the in vitro and in vivo antitumor activities of phosphorylated mitomycin C and etoposide derivatives by monoclonal antibody-alkaline phosphatase conjugates. Cancer Res 49:5789-5792.
161. Senter PD, Su PC, Katsuragi T, Sakai T, Cosand WL, Hellstrom I, and Hellstrom KE (1991) Generation of 5-fluorouracil from 5-fluorocytosine by monoclonal antibody-cytosine deaminase conjugates. Bioconjug Chem 2:447-451.
162. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423.
163. Shimma N, Umeda I, Arasaki M, Murasaki C, Masubuchi K, Kohchi Y, Miwa M, Ura M, Sawada N, Tahara H, et al. (2000) The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine. Bioorg Med Chem 8:1697-1706.
164. Shou M, Lin Y, Lu P, Tang C, Mei Q, Cui D, Tang W, Ngui JS, Lin CC, Singh R, et al. (2001) Enzyme kinetics of cytochrome P450-mediated reactions. Curr Drug Metab 2:17-36.
165. Siegel D, Gibson NW, Preusch PC, 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.
166. Simonova M, Wall A, Weissleder R, and Bogdanov A Jr (2000) Tyrosinase mutants are capable of prodrug activation in transfected nonmelanotic cells. Cancer Res 60:6656-6662.
167. Singhal S and Kaiser LR (1998) Cancer chemotherapy using suicide genes. Surg Oncol Clin North Am 7:505-536.
168. Smythe WR (2000) Prodrug/drug sensitivity gene therapy: current status. Curr Oncol Rep 2:17-22.
169. Soda K (1987) Microbial sulfur amino acids: an overview. Methods Enzymol 143:453-459.
170. Sorscher EJ, Peng S, Bebok Z, Allan PW, Bennett LL Jr, and Parker WB (1994) Tumor cell bystander killing in colonic carcinoma utilizing the Escherichia coli DeoD gene to generate toxic purines. Gene Ther 1:233-238.
171. Spanswick VJ, Cummings J, and Smyth JF (1998) Current issues in the enzymology of mitomycin C metabolic activation. Gen Pharmacol 31:539-544.
172. Spatzenegger M and Jaeger W (1995) Clinical importance of hepatic cytochrome P450 in drug metabolism. Drug Metab Rev 27:397-417.
173. Sperker B, Backman JT, and Kroemer HK (1997a) The role of beta-glucuronidase in drug disposition and drug targeting in humans. Clin Pharmacokinet 33:18-31.
174. Sperker B, Murdter TE, Schick M, Eckhardt K, Bosslet K, and Kroemer HK (1997b) Interindividual variability in expression and activity of human beta-glucuronidase in liver and kidney: consequences for drug metabolism. J Pharmacol Exp Ther 281:914-920.
175. Stavrovskaya AA (2000) Cellular mechanisms of multidrug resistance of tumor cells. Biochemistry (Mosc) 65:95-106.
176. Stegman LD, Zheng H, Neal ER, Ben-Yoseph O, Pollegioni L, Pilone MS, and Ross BD (1998) Induction of cytotoxic oxidative stress by D-alanine in brain tumor cells expressing Rhodotorula gracilis D-amino acid oxidase: a cancer gene therapy. Hum Gene Ther 9:185-193.
177. Stevens JL (1985) Isolation and characterization of a rat liver enzyme with both cysteine conjugate b-lyase and kynureninase activity. J Biol Chem 260:7945-7950.
178. Stevens JL, Robbins JD, and Byrd RA (1986) A purified cysteine conjugate beta-lyase from rat kidney cytosol. Requirement for an alpha-keto acid of an amino acid oxidase for activity and identity with soluble glutamine transaminase K. J Biol Chem 261:15529-15537.
179. Strange RC, Spiteri MA, Ramachandran S, and Fryer AA (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482:21-26.
180. Sugata S, Kono A, Hara Y, Karube Y, and Matsushima Y (1986) Partial purification of a thymidine phosphorylase from human gastric cancer. Chem Pharm Bull (Tokyo) 34:1219-1222.
181. Sun W and Haller D (2001) UFT in the treatment of colorectal and breast cancer. Oncology (Huntingt) 15 (Suppl 2):49-56.
182. Suresh Kumar G, Lipman R, Cummings J, and Tomasz M (1997) Mitomycin C-DNA adducts generated by DT-diaphorase. Revised mechanism of the enzymatic reductive activation of mitomycin C. Biochemistry 36:14128-14136.
183. Svensson HP, Frank IS, Berry KK, and Senter PD (1998) Therapeutic effects of monoclonal antibody-beta-lactamase conjugates in combination with a nitrogen mustard anticancer prodrug in models of human renal cell carcinoma. J Med Chem 41:1507-1512.
184. Svensson HP, Kadow JF, Vrudhula VM, Wallace PM, and Senter PD (1992) Monoclonal antibody-beta-lactamase conjugates for the activation of a cephalosporin mustard prodrug. Bioconjug Chem 3:176-181.
185. Svensson HP, Vrudhula VM, Emswiler JE, MacMaster JF, Cosand WL, Senter PD, and Wallace PM (1995) In vitro and in vivo activities of a doxorubicin prodrug in combination with monoclonal antibody beta-lactamase conjugates. Cancer Res 55:2357-2365.
186. Syrigos KN and Epenetos AA (1999) Antibody directed enzyme prodrug therapy (ADEPT): a review of the experimental and clinical considerations. Anticancer Res 19:605-613.
187. Takasuna K, Hagiwara T, Hirohashi M, Kato M, Nomura M, Nagai E, Yokoi T, and Kamataki T (1996) Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res 56:3752-3757.
188. Tateishi M, Suzuki S, and Shimizu H (1978) Cysteine conjugate β-lyase in rat liver. A novel enzyme catalyzing formation of thiol-containing metabolites of drugs. J Biol Chem 253:8854-8859.
189. Thomas PD, Kishi H, Cao H, Ota M, Yamashita T, Singh S, and Jimbow K (1999) Selective incorporation and specific cytocidal effect as the cellular basis for the antimelanoma action of sulphur containing tyrosine analogs. J Investig Dermatol 113:928-934.
190. Toft NJ, Sansom OJ, Brookes RA, Arends MJ, Wood M, Margison GP, Winton DJ, and Clarke AR (2000) In vivo administration of O(6)-benzylguanine does not influence apoptosis or mutation frequency following DNA damage in the murine intestine, but does inhibit P450-dependent activation of dacarbazine. Carcinogenesis 21:593-598.
191. Tomasz M (1995) Mitomycin C: small, fast and deadly (but very selective). Chem Biol 2:575-579.
192. Tomisawa H, Ichihara S, Fukazawa H, Ichimoto N, Tateishi M, and Yamamoto I (1986) Purification and characterization of human hepatic cysteine-conjugate beta-lyase. Biochem J 235:569-575.
193. Ueda Y, Wong H, Matiskella JD, Mikkilineni AB, Farina V, Fairchild C, Rose WC, Mamber SW, Long BH, Kerns EH, et al. (1994) Synthesis and antitumor evaluation of 2′-oxycarbonylpaclitaxels (paclitaxel-2′-carbonates). Bioorg Med Chem Lett 4:1861-1864.
194. Vainio H (1980) Role of hepatic metabolism, in Concepts in Drug Metabolism (Testa B and Jenner P eds) pp 251-284, Marcel Dekker, Inc., New York.
195. van Bladeren PJ (2000) Glutathione conjugation as a bioactivation reaction. Chem Biol Interact 129:61-76.
196. Van Hoof VO and De Broe ME (1994) Interpretation and clinical significance of alkaline phosphatase isoenzyme patterns. Crit Rev Clin Lab Sci 31:197-293.
197. Vielkind U, Schlage W, and Anders F (1977) Melanogenesis in genetically determined pigment cell tumors of platyfish and platyfish-swordtail hybrids: correlation between tyrosine activity and degree of malignancy. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 90:285-299.
198. Vrudhula VM, Senter PD, Fischer KJ, and Wallace PM (1993a) Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate. J Med Chem 36:919-923.
199. Vrudhula VM, Svensson HP, Kennedy KA, Senter PD, and Wallace PM (1993b) Antitumor activities of a cephalosporin prodrug in combination with monoclonal antibody-beta-lactamase conjugates. Bioconjug Chem 4:334-340.
200. Vrudhula VM, Svensson HP, and Senter PD (1995) Cephalosporin derivatives of doxorubicin as prodrugs for activation by monoclonal antibody-beta-lactamase conjugates. J Med Chem 38:1380-1385.
201. Vrudhula VM, Svensson HP, and Senter PD (1997) Immunologically specific activation of a cephalosporin derivative of mitomycin C by monoclonal antibody β-lactamase conjugates. J Med Chem 40:2788-2792.
202. Wadkins RM, Morton CL, Weeks JK, Oliver L, Wierdl M, Danks MK, and Potter PM (2001) Structural constraints affect the metabolism of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) by carboxylesterases. Mol Pharmacol 60:355-362.
203. Wallace PM and Senter PD (1991) In vitro and in vivo activities of monoclonal antibody-alkaline phosphatase conjugates in combination with phenol mustard phosphate. Bioconjug Chem 2:349-352.
204. Walsh CT, Schonbrunn A, and Abeles RH (1971) Studies on the mechanism of action of D-amino acid oxidase. Evidence for removal of substrate α-hydrogen as a proton. J Biol Chem 246:6855-6866.
205. Walton MI, Smith PJ, and Workman P (1991) The role of NAD(P)H: quinone reductase (EC 1.6.99.2, DT-diaphorase) in the reductive bioactivation of the novel indaloquinone antitumor agent EO9. Cancer Commun 3:199-206.
206. Walton MI, Sugget N, and Workman P (1992) The role of human and rodent DT-diaphorase in the reductive metabolism of hypoxic cell cytotoxins. Int J Radiat Oncol Biol Phys 22:643-647.
207. Walton MI, Wolf CR, and Workman P (1989) Molecular enzymology of the reductive bioactivation of hypoxic cell cytotoxins. Int J Radiat Oncol Biol Phys 16:983-986.
208. Waxman DJ, Chen L, Hecht JE, and Jounaidi Y (1999) Cytochrome P450-based cancer gene therapy: recent advances and future prospects. Drug Metab Rev 31:503-522.
209. Wierdl M, Morton CL, Weeks JK, Danks MK, Harris LC, and Potter PM (2001) Sensitization of human tumor cells to CPT-11 via adenoviral-mediated delivery of a rabbit liver carboxylesterase. Cancer Res 61:5078-5082.
210. Winski SL, Swann E, Hargreaves RH, Dehn DL, Butler J, Moody CJ, 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.
211. Wintersberger E (1997) Regulation and biological function of thymidine kinase. Biochem Soc Trans 25:303-308.
212. Woodland C, Ito S, Granvil CP, Wainer IW, Klein J, and Koren G (2000) Evidence of renal metabolism of ifosfamide to nephrotoxic metabolites. Life Sci 68:109-117.
213. Workman P, Walton MI, Powis G, and Schlager JJ (1989) DT-diaphorase: questionable role in mitomycin C resistance, but a target for novel bioreductive drugs? Br J Cancer 60:800-803.
214. Wormhoudt LW, Commandeur JN, and Vermeulen NP (1999) Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione-S-transferase and epoxide hydrolase enzymes: relevance to xenobiotic metabolism and toxicity. Crit Rev Toxicol 29:59-124.
215. Yamazaki H, Komatsu T, Takemoto K, Shimada N, Nakajima M, and Yokoi T (2001) Rat cytochrome p450 1A and 3A enzymes involved in bioactivation of tegafur to 5-fluorouracil and autoinduced by tegafur in liver microsomes. Drug Metab Dispos 29:794-797.
216. Yoshimura A, Kuwazuru Y, Furukawa T, Yoshida H, Yamada K, and Akiyama S (1990) Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors. Biochim Biophys Acta 1034:107-113.
217. Yu LJ, Matias J, Scudiero DA, Hite KM, Monks A, Sausville EA, and Waxman DJ (2001) P450 enzyme expression patterns in the NCI human tumor cell line panel. Drug Metab Dispos 29:304-312.
218. Yuhas JM (1980) Active versus passive absorption kinetics as the basis for selective protection of normal tissues by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res 40:1519-1524.
219. Zhu Z, Jiang W, Ganther HE, Ip C, and Thompson HJ (2000) In vitro effects of Se-allylselenocysteine and Se-propylselenocysteine on cell growth, DNA integrity and apoptosis. Biochem Pharmacol 60:1467-1473.
220. Zimmerman M and Seidenberg J (1964) Deoxyribosyl transfer. I. Thymidine phosphorylase and nucleoside deoxyribosyltransferase in normal and malignant tissues. J Biol Chem 239:2618-2621.