Human cytochrome P450-catalyzed conversion of the proestrogenic pesticlde methoxychlor into an estrogen: Role of CYP2C19 and CYP1A2 in O- demethylation

Drug Metabolism and Disposition

Volumn 26, Issue 9, 1998, Pages 868-874

  Stresser, David M ^b   Kupfer, David ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450; ESTROGEN; METHOXYCHLOR; PESTICIDE;

ARTICLE; DRUG METABOLISM; ENZYME ACTIVITY; ESTROGEN ACTIVITY; HUMAN; HUMAN TISSUE; INSECT; LIVER MICROSOME; PRIORITY JOURNAL;

ANIMALS; ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP1A2; CYTOCHROME P-450 ENZYME SYSTEM; DEALKYLATION; ENZYME INHIBITORS; ESTRADIOL CONGENERS; HUMANS; INSECTICIDES; ISOENZYMES; KINETICS; MALE; METHOXYCHLOR; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; RATS; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS; REGRESSION ANALYSIS;

EID: 0031657035     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (38)

1. Bulger WH, Feil VJ and Kupfer D (1985) Role of hepatic mono-oxygenases in generating estrogenic metabolites from methoxychlor and from its identified contaminants. Mol Pharmacol 27:115-124.
2. Bulger WH and Kupfer D (1985) Estrogenic activity of pesticides and other xenobiotics on the uterus and male reproductive tract, in Endocrine Toxicology (Thomas JA, Korach KS and McLachlan JA, eds) pp 1-33, Raven Press, New York.
3. Bulger WH and Kupfer D (1989) Characteristics of monooxygenase-mediated covalent binding of methoxychlor in human and rat liver microsomes. Drug Metab Dispos 17:487-494.
4. Bulger WH, Muccitelli RM and Kupfer D (1978) Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites: role of hepatic mono-oxygenases in methoxychlor activation. Biochem Pharmacol 27:2417-2423.
5. Burstein SH and Kupfer D (1971) Hydroxylation of trans delta-1-tetrahydrocannabinol by hepatic microsomal oxygenase. Ann NY Acad Sci 191:61-67.
6. Chapin RE, Harris MW, Davis BJ, Ward SM, Wilson RE, Mauney MA, Lockhart AC, Smialowicz RJ, Moser VC, Burka LT and Collins BJ (1997) The effects of perinatal/juvenile methoxychlor exposure on adult rat nervous, immune, and reproductive system function. Fundam Appl Toxicol 40:138-157.
7. Chauret N, Gauthier A, Martin J and Nicoll-Griffith DA (1997) In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat and horse. Drug Metab Dispos 25:1130-1136.
8. Cummings AM (1997) Methoxychlor as a model for environmental estrogens. Crit Rev Toxicol 27:367-379.
9. Davison KH, Lamoureux CH and Feil VJ (1982) Methoxychlor metabolism in goats. J Agric Food Chem 30:130-137.
10. Dehal SS and Kupfer D (1994) Metabolism of the proestrogenic pesticide methoxychlor by hepatic P450 monooxygenases in rats and humans: Dual pathways involving novel ortho ring-hydroxylation by CYP2B. Drug Metab Dispos 22:937-946.
11. Distlerath LM, Reilly PEB, Martin MV, Davis GG, Wilkinson GR and Guengerich FP (1985) Purification and characterization of the human liver cytochromes P-450 involved in debrisoquine 4-hydroxylation and phenacetin O-deethylation, two prototypes for genetic polymorphism in oxidative drug metabolism. J Biol Chem 260:9057-9067.
12. Draper AJ, Madan. A and Parkinson A (1997) Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch Biochem Biophys 341:47-61.
13. Gardner DR and Bailey JR (1975) Methoxychlor: its effects on environmental quality. National Research Council of Canada Report No. 14102, NRCC/CNRC, Ottawa, Canada.
14. Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, Lasker JM and Ghanayem BI (1994) Evidence that CYP2C19 is the major (S)-mephenytoin 4′-hydroxylase in humans. Biochemistry 33:1743-1752.
15. Hodge HC, Maynard EA, Thomas JF, Blanchet JHJ, Wilt JWG and Mason KE (1950) Short-term oral toxicity tests of methoxychlor (2,2 di-(p-methoxy phenyl)-1,1,1-trichlorethane) in rats and dogs. J Pharmacol Exp Ther 99:140-148.
16. Inaba T, Jurima M, Mahon WA and Kalow W (1985) In vitro inhibition studies of two isozymes of human liver cytochrome P-450: mephenytoin p-hydroxylase and sparteine monooxygenase. Drug Metab Dispos 13:443-448.
17. June F, Richardson TH, Raucy JL and Johnson EF (1997) Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P450 2C18 and P450 2C19 as low Km diazepam N-demethylases Drug Metab Dispos 25:133-139.
18. Kapoor IP, Metcalf RL, Nystrom RF and Sangha GK (1970) Comparative metabolism of methoxychlor, methiochlor and DDT in mouse, insects and in a model ecosystem. J Agric Food Chem 18:1145-1152.
19. Kishimoto D and Kurihara N (1996) Effects of cytochrome P450 antibodies on the oxidative demethylation of methoxychlor catalyzed by rat liver microsomal cytochrome P450 isozymes: Isozyme specificity and alteration of enantiotopic selectivity. Pestic Biochem Physiol 51:44-52.
20. Kishimoto D, Oku A and Kurihara N (1995) Enantiotopic selectivity of cytochrome P450-catalyzed oxidative demethylation of methoxychlor: Alteration of selectivity depending on isozymes and substrate concentrations. Pestic Biochem Physiol 51:12-19.
21. Kupfer D, Bulger WH and Theoharides AD (1990) Metabolism of methoxychlor by hepatic P-450 monooxygenases in rat and human. 1. Characterization of a novel catechol metabolite. Chem Res Toxicol 3:8-16.
22. Lowry OH, Rosebrough NJ, Farr AL and Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265-275.
23. Miles JS, McLaren AW, Forrester LM, Glancey MJ, Lang MA and Wolf CR (1990) Identification of the human liver cytochrome P450 responsible for coumarin 7-hydroxylase activity. Biochem J 267:365-371.
24. Newton DJ, Wang RW and Lu AY (1995) Cytochrome P450 inhibitors: Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23:154-158.
25. Ousterhout J, Struck RF and Nelson JA (1981) Estrogenic activities of methoxychlor metabolites. Biochem Pharmacol 30:2869-2871.
26. Rane A, Wilkinson GR and Shand DG (1977) Prediction of hepatic extraction ratio from in vitro measurement of intrinsic clearance. J Pharmacol Exp Ther 200:420-424.
27. Raucy JL, Wester MR, Aramsombatdee E and Lasker JM (1994) Purification and characterization of human liver CYP2C19: an S-mephenytoin 4′ hydroxylase, in Xth International Symposium on Microsomes and Drug Oxidations, Toronto, Canada, Abstract, July 1994.
28. Reuber MD (1980) Carcinogenicity and toxicity of methoxychlor. Environ Health Perspec 36:205-219.
29. 14C]Naproxen O-demethylase activity in human liver microsomes: Evidence for the involvement of cytochrome P4501A2 and P4502C9/10. Drug Metab Dispos 24:126-136.
30. Schlenk D, Stresser DM, McCants JC, Nimrod AC and Benson WH (1997) Influence of β-naphthoflavone and methoxychlor pretreatment on the biotransformation and estrogenic activity of methoxychlor in channel catfish (Ictalurus punctatus). Toxicol Appl Pharmacol 145:349-356.
31. Shimada T, Gillam EMJ, Sutter TR, Strickland PT, Guengerich FP and Yamazaki H (1997) Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos 25:617-622.
32. 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.
33. Stauffer CE (1975) A linear curve for the Folin Lowry determination of protein. Anal Biochem 69:646-648.
34. Stresser DM, Dehal SS and Kupfer D (1996) Ring hydroxylation of [o-3H]methoxychlor as a probe for liver microsomal CYP2B activity: a potential assay for CYP2B in vivo. Anal Biochem 233:100-107.
35. Stresser DM and Kupfer D (1997) Catalytic characteristics of CYP3A4: requirement for a phenolic function in ortho hydroxylation of estradiol and mono-O-demethylated methoxychlor. Biochemistry 36:2203-2210.
36. Stresser DM and Kupfer D (1998) Prosubstrates of CYP3A4, the major human hepatic cytochrome P450: transformation into substrates by other P450 isoforms. Biochem Pharmacol, in press.
37. Wrighton SA, Stevens JC, Becker GW and Vandenbranden M (1993) Isolation and characterization of human liver cytochrome P450 2C19: Correlation between 2C19 and S-mephenytoin 4′-hydroxylation Arch Biochem Biophys 306:240-245.
38. Yamano S, Tatsuno J and Gonzalez FJ (1990) The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. Biochemistry 29:1322-1329.