Rat Hepatic Microsomal Metabolism of Ethylenethiourea. Contributions of the Flavin-Containing Monooxygenase and Cytochrome P-450 Isozymes

Chemical Research in Toxicology

Volumn 4, Issue 4, 1991, Pages 482-489

  Decker, Caroline J ^a   Doerge, Daniel R ^a  

^a UNIVERSITY OF HAWAII   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 IMIDAZOLIDINETHIONE; CYTOCHROME P450 ISOENZYME; UNSPECIFIC MONOOXYGENASE;

ANIMAL TISSUE; ARTICLE; COVALENT BOND; DNA BINDING; ENZYME INACTIVATION; LIVER MICROSOME; MALE; NONHUMAN; RAT; XENOBIOTIC METABOLISM;

ANIMAL; CYTOCHROME P-450 ENZYME SYSTEM; DITHIOTHREITOL; DNA; ETHYLENETHIOUREA; GLUTATHIONE; HEME; ISOENZYMES; MALE; MICROSOMES, LIVER; NADP; OXYGENASES; PROTEIN BINDING; RATS; RATS, INBRED STRAINS; SUPPORT, U.S. GOV'T, P.H.S.;

ANIMALIA;

EID: 0026045001     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx00022a013     Document Type: Article

References (46)

1. U.S. Environmental Protection Agency (1989) Ethylenebisthiocarbamates; Notice of preliminary determination to cancel certain registrations, notice of availability of technical support document and draft notice of intent to cancel. Fed. Regist. 54, 52158–52185.
2. Hunter, A. I., and Neal, R. A. (1975) Inhibition of hepatic mixedfunction oxidase activity in vitro and in vivo by various thionosulfurcontaining compounds. Biochem. Pharmacol. 24, 2199–2205.
3. Poulsen, L. I., Hyslop, R. M., and Ziegler, D. M. (1979) S-Oxygenation of N-substituŧed thioureas catalyzed by the pig liver microsomal FAD-containting monooxygenase. Arch. Biochem. Biophys. 198, 78–88.
4. Ziegler, D. M. (1980) Microsomal flavincontaining monooxygenase: Oxygenation of nucleophilic nitrogen and sulfur compounds. In Bioactiυation of Foreign Compounds (Jacoby, W. B., Ed.) pp 201–230, Academic Press, New York.
5. Ziegler, D. M. (1988) Flavincontaining monooxygenase: Catalytic mechanism and substrate specificities. Drug Metab. Reυ. 19, 1–32.
6. Neal, R. A. (1980) Microsomal metabolism of thionosulfur compounds: Mechanisms and toxicological significance. Reυ. Biochem. Toxicol. 2, 131–171.
7. Decker, C. J., Rashed, M. S., Baillie, T. A., Maltby, D., and Correia, M. A. (1989) Oxidative metabolism of spironolactone: Evidence for the involvement of electrophilic thiosteroid species in drugmediated destruction of rat hepatic cytochrome P-450. Biochemistry 28, 5128–5136.
8. Decker, C. J., Cashman, J. R., Sugiyama, K., Maltby, D., and Correia, M. A. Formation of glutathionylspironolactone disulfide by rat liver cytochromes P-450 or hog liver flavin monoxygenases: A functional probe of two electron oxidations of the thiosteroid? (submitted for publication).
9. Tynes, R. E., and Hodgson, E. (1983) Oxidation of thiobenzamide by the FAD-containing and cytochrome P-450-dependent monooxygenases of liver and lung microsomes. Biochem. Pharmacol. 32, 3419–3428.
10. Chieli, E., and Malvaldi, G. (1984) Role of the microsomal FAD-containing monooxygenase in the liver toxicity of thioacetamide S-Oxide. Toxicology 31, 41–52.
11. Kamataki, T., and Neal, R. A. (1976). Metabolism of diethyl pnitrophenyl phosphorothionate (parathion) by a reconstituted mixedfunction oxidase enzyme system: Studies of the covalent binding of the sulfur atom. Mol. Pharmacol. 12, 933–944.
12. Dalvi, R. R., Poore, R. E., and Neal, R. A. (1974). Studies of the metabolism of carbon disulfide by rat liver microsomes. Life Sci. 14, 1785–1796.
13. Lee, P. W., and Neal, R. A. (1978) Metabolism of methimazole by rat liver cytochrome P-450-containing monoxygenases. Drug Metab. Dispos. 6, 591–600.
14. Kedderis, G. I., and Rickert, D. E. (1983) Inhibition of the microsomal N-hydroxylation of 2-amino-6-nitrotoluene by a metabolite of methimazole. Biochem. Biophys. Res. Commun. 112, 433–438.
15. Kedderis, G. I., and Rickert, D. E. (1985) Loss of rat liver microsomal cytochrome P-450 during methimazole metabolism. Role of flavincontaining monooxygenase. Drug Metab. Dispos. 13, 58–61.
16. Doerge, D. R., Cooray, N. M., Yee, A. B. K., and Niemczura, W. P. (1990) Synthesis of isotopicallylabelled ethylenethiourea. J. Labelled Compd. Radiopharm. 28, 739–742.
17. Campbell, C. D., and Rees, C. W. (1969) Reactive intermediates. Part i. Synthesis and oxidation of 1- and 2-aminobenzotriazole. J. Chem. Soc. C., 742–747.
18. Lowry, O. H., Rosebrough, N. J., Farr, A. I., and Randall, R. J. (1951) Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265–275.
19. Nash, T. (1953) The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem. J. 55, 416–422.
20. Netter, K. J., and Seidel, G. (1964) An adaptively stimulated O-demethylating system in rat liver microsomes and its kinetic properties. J. Pharmacol. Exp. Ther. 146, 61–65.
21. Masters, B. S. S., Baron, J., Taylor, W. E., Isaacson, E. I., and LoSpalluto, J. (1971) Immunochemical studies on electron transport chains involving cytochrome P-450. J. Biol. Chem. 246, 4143–4150.
22. Iii H.K. E., and Burk, R. F. (1982) Effect of selenium deficiency and vitamin E deficiency on glutathione metabolism in isolated rat hepatocytes. J. Biol. Chem. 257, 10668–10672.
23. Kaplowitz, N. (1977) Interaction of azathioprine and glutathione in the liver of the rat. J. Pharmacol. Exp. Ther. 200, 479–486.
24. Estabrook, R. W., Peterson, J. K., and Hildebrandt, A. (1972) The spectrophotometric measurement of turbid suspensions of cytochrome associated with drug metabolism. Methods Pharmacol. 2, 303–350.
25. Omura, T., and Sato, R. (1964) The carbon monoxidebinding pigment of liver microsomes I. Evidence for its hemoprotein nature. J. Biol. Chem. 239, 2370–2378.
26. Corbett, M. D., Lim, L. O., Corbett, B. R., Johnston, J. J., and Wiebkin, P. (1988) Covalent binding of N-hydroxy-N-acetyl-2-aminofluorene and N-hydroxy-N-glycolyl-2-aminofluorene to rat hepatocyte DNA: In vitro and cellsuspension studies. Chem. Res. Toxicol. 1, 41–46.
27. Doerge, D. R., and Takazawa, R. S. (1990) Mechanism of thyroid peroxidase inhibition by ethylenethiourea. Chem. Res. Toxicol. 3, 98–101.
28. Guengerich, F. P., Dannan, G. A., Wright, S. T., Martin, M. V., and Kaminsky, L. S. (1982) Purification and characterization of liver microsomal cytochromes P-450: Electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phénobarbital or ßnaphthoflavone. Biochemistry 21, 6019–6030.
29. Guengerich, F. P. (1987) Enzymology of rat liver cytochromes P-450. In Mammalian Cytochromes P-450 (Guengerich, F. P., Ed.) Vol. I, pp 2–39, CRC Press, Boca Raton, FL.
30. Wrighton, S. A., Maurel, P., Scheutz, E. G., Watkins, P. B., Young, B., and Guzelian, P. S. (1985) Identification of the cytochrome P-450 induced by macrolide antibiotics in rat liver as the glucocorticoid responsive cytochrome P450. Biochemistry 24, 2171–2178.
31. Nebert, D. W., Adesnik, M., Coon, M. J., Estabrook, R. W., Gonzalez, F. J., Guengerich, F. P., Gunsalus, I. C., Johnson, E. F., Kemper, B., Levin, W., Phillips, I. R., Sato, R., and Waterman, M. R. (1989) The P-450 gene superfamily: Recommended nomenclature. DNA 6, 1–11.
32. Sum, C. Y., and Kasper, C. B. (1982) Mixedfunction amine oxidase of the rat hepatocyte nuclear envelope. Demonstration and effects of phénobarbital and 3-methylcholanthrene. Biochem. Pharmacol. 31, 69–73.
33. Devereaux, T. R., and Fouts, J. R. (1975) Effect of pregnancy or treatment with certain steroids on N, N-dimethylaniline demethylation and N-oxidation by rabbit liver or lung microsomes. Drug Metab. Dispos. 3, 254–258.
34. Ortiz de Montellano, P. R., and Mathews, J. M. (1981) Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole. Biochem. J. 195, 761–764.
35. Gudzinowicz, M. J., and Neal, R. A. (1981) Differentiation of rat liver microsomal amine oxidase and cytochrome P-450 catalyzed metabolism of thioacetamide and thioacetamide S-Oxide. Toxicologist 1, 67.
36. Ortiz de Montellano, P. R. (1988) Suicide substrates for drug metabolizing enzymes: Mechanisms and biological consequences. Prog. Drug Metab. 2, 99–148.
37. Dalvi, R. R., Hunter, A. I., and Neal, R. A. (1975) Toxicological implications of the mixedfunction oxidase catalyzed metabolism of carbon disulfide. Chem.-Biol. Interact. 10, 347–361.
38. Miller, G. E., Zemaitis, M. A., and Greene, F. E. (1983) Mechanisms of diethyldithiocarbabateinduced loss of cytochrome P-450 from rat liver. Biochem. Pharmacol. 16, 2433–2442.
39. Cashman, J. R. (1987) A Convenient radiometric assay for flavincontaining monooxygenase activity. Anal. Biochem. 160, 294–300.
40. Mathews, J. M., and Bend, J. R. (1986) N-Alkylaminobenzotriazoles as isozymeselective suicide inhibitors of rabbit pulmonary microsomal cytochrome P-450. Mol. Pharmacol. 30, 25–32.
41. El-Hawari, A. M., and Plaa, G. L. (1977) α-Naphthylisothiocyanate (ANIT) hepatotoxicity and irreversible binding to rat liver microsomes. Biochem. Pharmacol. 26, 1857–1866.
42. Hyslop, R. M., and Jardine, I. (1981) Metabolism of 6-thiopurines. I. Irreversible binding of a metabolite of 6-thiopurine to mammalian hepatic protein in vitro. J. Pharmacol. Exp. Ther. 218, 621–628.
43. Halpert, J., Hammond, D., and Neal, R. A. (1980) Inactivation of purified rat liver cytochrome P-450 during the metabolism of parathion (diethyl pnitrophenyl phosphorothionate). J. Biol. Chem. 255, 1080–1089.
44. Krieter, P. A., Ziegler, D. M., Hiii, K. A., and Burk, R. F. (1984) Increased biliary GSSG efflux from rat livers perfused with thiocarbamide substrates for the flavincontaining monooxygenase. Mol. Pharmacol. 26, 122–127.
45. Williams, C. H. (1976) Flavincontaining dehydrogenases. In The Enzymes (Boyer, P. D., Ed.) Vol. 13, pp 89–173, Academic Press, New York.
46. Sies, H., and Gerstenecker, C. (1972) Oxidation in the NADP system and release of GSSG from hemoglobinfree perfused rat liver during peroxidatic oxidation of glutathione by hydroperoxides. FEBS Lett. 27, 171–175.