Cytochrome P-450 3A and 2D6 catalyze ortho hydroxylation of 4- hydroxytamoxifen and 3-hydroxytamoxifen (droloxifene) yielding tamoxifen catechol: Involvement of catechols in covalent binding to hepatic proteins

Drug Metabolism and Disposition

Volumn 27, Issue 6, 1999, Pages 681-688

  Dehal, Shangara S ^a   Kupfer, David ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 HYDROXYTAMOXIFEN; CATECHOL; CYTOCHROME P450 ISOENZYME; DEBRISOQUINE 4 HYDROXYLASE; DROLOXIFENE; LIVER PROTEIN; TAMOXIFEN DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CATALYSIS; COVALENT BOND; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG PROTEIN BINDING; ENZYME INHIBITION; INTRAPERITONEAL DRUG ADMINISTRATION; LIVER MICROSOME; NONHUMAN; PRIORITY JOURNAL; RAT;

ANIMALS; BIOTRANSFORMATION; CATECHOLS; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 ENZYME SYSTEM; ESTROGEN ANTAGONISTS; HUMANS; HYDROXYLATION; LIVER; MIXED FUNCTION OXYGENASES; PENTOBARBITAL; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; TAMOXIFEN;

ANIMALIA; INSECTA; STAPHYLOCOCCUS PHAGE 3A;

EID: 0033017135     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (40)

1. Aoyama T, Korzekwa W, Nagata K, Gillette J, Gelboin HV and Gonzalez FJ (1990) Estradiol metabolism by complementary deoxyribonucleic acid-expressed human cytochrome P-450. Endocrinology 126:3101-3106.
2. Borgna, J-L and Rochefort H (1981) Hydroxylated metabolites of tamoxifen aie formed in vivo and bound to estrogen receptor in target tissues. J Biol Chem 256:859-868.
3. Burstein SH and Kupfer D (1971) Hydroxylation of trans-δ-tetrahydrocannabinol by hepatic microsomal oxygenase. Ann Ny Acad Sci 191:61-67.
4. Crewe HK, Ellis SW, Lennard MS and Tucker GT (1997) Variable contribution of cytochrome P450 2D6, 2C9 and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes. Biochem Pharmacol 53:171-178.
5. Dehal SS and Kupfer D (1996) Evidence that the catechol 3,4-dihydroxytamofen is a proximate intermediate to the reactive species binding covalently to proteins. Cancer Res 56:1283-1290.
6. Dehal SS and Kupfer D (1997) CYP2D6 catalyzes tamoxifen-4-hydroxylation in human liver. Cancer Res 57:3402-3406.
7. 5 and phospholipid with unsaturated fatty acids. Arch Biochem Biophys 291:231-240.
8. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L and Wolmark N (1998) Tamoxifen for prevention of breast cancer: Report of the national surgical adjuvant breast and bowl project -1 study. J Nat Cancer lnst 90:1371-1388.
9. Foster AB, Griggs LJ, Jarman M, vanMaanen MS and Schulten H-R (1980) Metabolism of tamoxifen by rat liver microsomes: Formation of the oxide, a new metabolite, Biochem Pharmacol 29:1977-1979.
10. Grace JM, Kinter MT and Mcdonald TL (1994) Atypical metabolism of deprenyl and its enantiomer, (S)-(+)-N,alpha-dimethyl-N-propylnylphenethylamine, by cytochrome P4502D6. Chem Res Toxicol 7:286-290.
11. Hoffman AR, Paul SM and Axelrod J (1980) Estrogen-2-hydroxylase in the rat. Biochem Pharmacol 29:83-87.
12. Jacolot F, Simon I, Dreano Y, Beaune P, Riche C and Berthou F (1991) Identification of the cytochrome P-450 IIIA family as the enzymes involved in the N-demethylation of tamoxifen in human liver microsomes. Biochem Pharmacol 41:1911-1919.
13. Jordan VC (1993) A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol 110:507-571.
14. Killackey MA, Hakes TB and Price VK (1985) Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens. Cancer Treat Rep 69:237-238.
15. King CM (1995) Tamoxifen and the induction of cancer. Carcinogenesis 16:1449-1454.
16. Kupfer D (1996) The covalent binding of tamoxifen to proteins and DNA, in Tamoxifen: Beyond the Antiestrogen (Kellen JA ed) pp 201-230, Birkhauser, Boston.
17. Kupfer D, Bulger WH and Theoharides AD (1990) Metabolism of methoxychlor by hepatic P-450 monooxygenases in rat and human. I .Characterization of a novel catechol metabolite. Chem Res Toxicol 3:8-16.
18. Kupfer D and Dehal SS (1996) Tamoxifen metabolism by microsomal cytochrome P450 and flavin-containing monooxygenase. Methods Enzymol 272:152-163.
19. AA as catalyst of 4-hydroxylation induced by TCDD and βNF. Cancer Res 54:3140-3144.
20. Mani C, Gelboin HV, Park SS, Pierce R, Parkinson A and Kupfer D (1993a) Metabolism of the antimammary cancer antiestrogenic agent tamoxifen, I. Cytochrome P-450-catalyzed N-demethylation and 4-hydroxylation. Drug Metab Dispos 21:645-656.
21. Mani C, Hodgsom E and Kupfer D (1993b) Metabolism of the antimammary cancer antiestrogenic agent tamoxifen. II. Flavin-containing monooxygenase-mediated N-oxidation. Drug Metab Dispos 21:657-661.
22. Mani C and Kupfer D (1991) Cytochrome P-450-mediated activation and irreversible binding of the antiestrogen tamoxifen to proteins in rat and human liver: Possible involvement of flavin-containing monooxygenases in tamoxifen activation. Cancer Res 51:6052-6058.
23. Mani C, Pierce R, Parkinson A and Kupfer D (1994) Involvement of cytochrome P-4503A in catalysis of tamoxifen activation and covalent binding to rat and human liver microsomes. Carcinogenesis 15:2715-2720.
24. Martucci CP and Fishman J (1993) P450 enzymes of estrogen metabolism. Pharmacol Ther 57:237-257.
25. McCague R and Seago A (1986) Aspects of metabolism of tamoxifen by rat liver microsomes. Biochem Pharmacol 35:827-834.
26. Nelson SD (1982) Metabolic activation and drug toxicity. J Med Chem 25:753-765.
27. Pathak DN, Pongracz K and Bodell WJ (1995) Microsomal and peroxidase activation of 4-hydroxy-tamoxifen to form DNA adducts: Comparison with DNA adducts formed in Sprague-Dawley rats treated with tamoxifen. Carcinogenesis 16:11-15.
28. 32P-postlabeling and use of metabolic inhibitors for two distinct pathways leading to mouse hepatic DNA adduct formation and identification of 4-hydroxytamoxifen as a proximate metabolite. Carcinogenesis 15:2087-2094.
29. Reunitz PC, Bagley JR and Pape CW (1984) Some chemical and biochemical aspects of liver microsomal metabolism of tamoxifen. Drug Metab Dispos 12:478-483.
30. Shimada T, Yamazaki H, Mimura M, lnui Y and Guengerich FP (1994) Interindividual variations in human liver cytochrome P450 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.
31. Shou M, Korzekwa KR, Brooks EN, Krausz KW, Gonzalez FJ and Gelboin HV (1997) Role of human hepatic cytochrome P450 1A2 and 3A4 in the metabolic activation of estrone. Carcinogenesis 18:207-214.
32. Skoda RC, Gonzalez FJ, Demierre A and Meyer UA (1988) Two mutant alleles of the human cytochrome P-450dbl gene (P450C2DI) associated with genetically deficient metabolism of debrisoquine and other drugs. Proc Natl Acad Sci USA 83:5240-5243.
33. Stresser D and Kupfer D (1997) Catalytic characteristics of CYP3A4: Requirement for phenolic function in ortho-hydroxylation of estradiol and O-demethylated methoxychlor. Biochemistry 36:2203-2210.
34. Tabakovic K, Gleason WB, Ojala WH and Abul-Hajj YJ (1996) Oxidative transformation of 2-hydroxyestrone. Stability and reactivity of 2,3-estrone quinone and its relationship to estrogen carcinogenicity. Chem Res Toxicol 9:860-865.
35. Turner MJ 3rd, Fields CE and Everman DB (1991) Evidence for superoxide formation during hepatic metabolism of tamoxifen. Biochem Pharmacol 41:1701-1705.
36. Vancutsem PM, Lazarus P and Williams GM (1994) Frequent and specific mutations of the rat p53 gene in hepatocarcinomas induced by tamoxifen. Cancer Res 54:3864-3867.
37. Williams GM, Iatropoulos MJ, Djordjevic MW and Kaltenberg OP (1993) The triphenylethylene drug tamoxifen is a strong carcinogen in the rat. Carcinogenesis 14:315-317.
38. Yager JD and Liehr JG (1996) Molecular mechanisms of estrogen carcinogenesis. Ann Rev Pharmacol Toxicol 36:203-232.
39. 5. J Biol Chem 271:27438-27444.
40. Zerilli A, Ratanasavanh D, Lucas D, Goasduff T, Dreano Y, Menard C, Picart D and Berthou F (1997) Both cytochromes P450 2E1 and 3A4 are involved in the o-hydroxylation of p-nitrophenol, a catalytic activity known to be specific for P450 2E1. Chem Res Toxicol 10:1205-1212.