Comparative in vitro metabolism of the suspected pro-oestrogenic compound, methoxychlor in precision-cut liver slices from male and female rats

Xenobiotica

Volumn 35, Issue 4, 2005, Pages 331-342

  Ohyama, K ^a   Maki, S ^a   Sato, K ^a   Kato, Y ^a  

^a INSTITUTE OF ENVIRONMENTAL TOXICOLOGY   (Japan)

Author keywords

Conjugation; Enantioselective metabolism; Metabolic activation; Oestrogenic responses; Oxidative demethylation; Sex differences

Indexed keywords

BISHYDROXYMETHOXYCHLOR 4 O SULFATE 4' O GLUCURONIDE; CARBON 14; DRUG METABOLITE; ESTROGEN; GLUCURONIDE; METHOXYCHLOR; MONOHYDROXYMETHOXYCHLOR GLUCURONIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONJUGATION; CONTROLLED STUDY; DEMETHYLATION; DOSE TIME EFFECT RELATION; DRUG METABOLISM; ESTROGEN ACTIVITY; FEMALE; GENDER; GLUCURONIDATION; IN VITRO STUDY; LIVER SLICE; MALE; METABOLIC REGULATION; METABOLITE; NONHUMAN; RAT; SEX DIFFERENCE; XENOBIOTIC METABOLISM;

ANIMALS; ESTROGENS; FEMALE; INSECTICIDES; LIVER; MALE; METABOLIC DETOXICATION, DRUG; METHOXYCHLOR; MICRODISSECTION; ORGAN CULTURE TECHNIQUES; RATS; RATS, INBRED F344; SEX FACTORS;

EID: 20944437614     PISSN: 00498254     EISSN: None     Source Type: Journal    
DOI: 10.1080/00498250500087309     Document Type: Article

References (35)

1. Barr J, Weir AJ, Brendel K, Sipes IG. 1991. Liver slices in dynamic organ culture. II. An in vitro cellular technique for the study of integrated drug metabolism using human tissue. Xenobiotica 21:341-350.
2. Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72:248-254.
3. Bulger WH, Muccitelli RM, Kupfer D. 1978a. Interactions of methoxychlor, methoxychlor base-soluble contaminant, and 2,2-bis(p-hydroxyphenyl)-1,1,1- trichloroethane with rat uterine estrogen receptor. Journal of Toxicology and Environmental Health 4:881-893.
4. Bulger WH, Muccitelli RM, Kupfer D. 1978b. Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites. Role of hepatic mono-oxygenase in methoxychlor activation. Biochemical Pharmacology 27:2417-2423.
5. Chapin RE, Harris MW, Davis BJ, Ward SM, Wilson RE, Mauney MA, Lockhart AC, Smialowicz RJ, Moser VC, Burka LT, Collins BJ. 1997. The effects of perinatal/juvenile methoxychlor exposure on adult rat nervous, immune, and reproductive system function. Fundamentals of Applied Toxicology 40:138-157.
6. Davison KL, Feil VJ, Lamoureux CH. 1982. Methoxychlor metabolism in goats. Journal of Agriculture and Food Chemistry 30:130-137.
7. Davison KL, Lamoureux CH, Feil VJ. 1983. Methoxychlor metabolism in goats. 2. Metabolites in bile and movement through skin. Journal of Agriculture and Food Chemistry 31:164-166.
8. Dehal SS, 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 Metabolism and Disposition 22:937-946.
9. Dogterom P. 1993. Development of a simple incubation system for metabolism studies with precision-cut liver slices. Drug Metabolism and Disposition 21:699-704.
10. Ekins S. 1996. Past, present, and future applications of precision-cut liver slices for in vitro xenobiotic metabolism. Drug Metabolism Reviews 28:591-623.
11. Elsby R, Maggs JL, Ashby J, Paton D, Sumpter JP, Park BK. 2001. Assessment of the effects of metabolism on the estrogenic activity of xenoestrogens: A two-stage approach coupling human liver microsomes and a yeast estrogenicity assay. Journal of Pharmacology and Experimental Therapeutics 296:329-337.
12. Gaido KW, Leonard LS, Lovell S, Gould JC, Babaï D, Portier CJ, McDonnell DP. 1997. Evaluation of chemicals with endocrine modulating activity in a yeast-based steroid hormone receptor gene transcription assay. Toxicology and Applied Pharmacology 143:205-212.
13. Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S. 2000. Interaction of methoxychlor and related compounds with estrogen receptor α and β, and androgen receptor: structure-activity studies. Molecular Pharmacology 58:852-858.
14. Gray LE, Jr, Ostby J, Ferrell J, Rehnberg G, Linder R, Cooper R, Goldman J, Slott V, Laskey J. 1989. A dose-response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. Fundamental and Applied Toxicology 12:92-108.
15. Hashemi E, Dobrota M, Till C, Ioannides C. 1999. Structural and functional integrity of precision-cut liver slices in xenobiotic metabolism: A comparison of the dynamic organ and multiwell plate culture procedures. Xenobiotica 29:11-25.
16. Hu Y, Krausz K, Gelboin HV, Kupfer D. 2004. CYP2C subfamily, primarily CYP2C9, catalyses the enantioselective demethylation of the endocrine disrupter pesticide methoxychlor in human liver microsomes: Use of inhibitory monoclonal antibodies in P450 identification. Xenobiotica 34:117-132.
17. Hu Y, Kupfer D. 2002a. Metabolism of the endocrine disrupter pesticide methoxychlor by human P450s: Pathways involving a novel catechol metabolite. Drug Metabolism and Disposition 30:1035-1042.
18. Hu Y, Kupfer D. 2002b. Enantioselective metabolism of the endocrine disruptor pesticide methoxychlor by human cytochromes P450 (P450s): Major differences in selective enantiomer formation by various P450 isoforms. Drug Metabolism and Disposition 30:1329-1336.
19. Ichinose R, Kurihara N. 1986. Deuterium and tritium isotope effects on the oxidative demethylation rate of methoxychlor in rat liver microsomes. Journal of Pesticide Science 11:231-236.
20. 3] methoxychlor in rat liver microsomes. Biochemical Pharmacology 36:3751-3756.
21. 3]methoxychlor and related deuterium-labeled compounds. Agricultural and Biological Chemistry 50:1331-1332.
22. Kapoor IP, Metcalf RL, Nystrom RF, Sangha GK. 1970. Comparative metabolism of methoxychlor, methiochlor, and DDT in mouse, insects, and in a model ecosystem. Journal of Agriculture and Food Chemistry 18:1145-1152.
23. Kishimoto D, Oku A, Kurihara N. 1995. Enantiotopic selectivity of cytochrome P450-catalyzed oxidative demethylation of methoxychlor: Alteration of selectivity depending on isozymes and substrate concentrations. Pesticide Biochemistry and Physiology 51:12-19.
24. Kurihara N, Oku A. 1991. Effects of added protein (bovine serum albumin) on the rate and enantiotopic selectivity of oxidative O-demethylation of methoxychlor in rat liver microsomes. Pesticide Biochemistry and Physiology 40:227-235.
25. Miyashita M, Shimada T, Nakagami S, Kurihara N, Miyagawa H, Akamatsu M. 2004. Enantioselective recognition of mono-demethylated methoxychlor metabolites by the estrogen receptor. Chemosphere 54:1273-1276.
26. Mugford CA, Kedderis GL. 1998. Sex-dependent metabolism of xenobiotics. Drug Metabolism Reviews 30:441-498.
27. 14C]methoxychlor in rat, mouse, Japanese quail and rainbow trout in precision-cut liver slices. Xenobiotica 34:741-754.
28. Ousterhout J, Struck RF, Nelson JA. 1981. Estrogenic activities of methoxychlor metabolites. Biochemical Pharmacology 30:2869-2871.
29. Shelby MD, Newblod RR, Tully DB, Chae K, Davis VL. 1996. Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. Environmental Health Perspectives 104:1296-1300.
30. Steensma A, Beamand JA, Walters DG, Price RJ, Lake BG. 1994, Metabolism of coumarin and 7-ethoxycoumarin by rat, mouse, guinea pig, Cynomolgus monkey and human precision-cut liver slices. Xenobiotica 24:893-907.
31. Stresser DM, Kupfer D. 1998a. Human cytochrome P450-catalyzed conversion of the proestrogenic pesticide methoxychlor into an estrogen. Role of CYP2C19 and CYP1A2 in O-demethylation. Drug Metabolism and Disposition 26:868-874.
32. Stresser DM, Kupfer D. 1998b. Prosubstrates of CYP3A4, the major human hepatic cytochrome P450. Transformation into substrates by other P450 isoforms. Biochemical Pharmacology 55:1861-1871.
33. Thompson DC, Perera K, London R. 1996, Metabolism and toxicity of 4-hydroxyphenylacetone in rat liver slices: Comparison with acetaminophen. Drug Metabolism and Disposition 24:866-871.
34. Walsh JS, Patanella JE, Halm KA, Facchine KL. 1995. An improved HPLC assay for the assessment of liver slice metabolic viability using 7-ethoxycoumarin. Drug Metabolism and Disposition 23:869-874.
35. Zalko D, Perdu-Durand E, Debrauwer L, Bec-Ferte M-P, Tulliez J. 1998. Comparative metabolism of clenbuterol by rat and bovine liver microsomes and slices. Drug Metabolism and Disposition 26:28-35.