Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지

Effects of Cigarette Smoke Condensate on the Activities of Xenobiotic Metabolizing Enzymes in Primary Cultured Rat Hepatocytes

  • Park, Mi-Jung (Department of Visual Optics, Seoul National Univeristy of Technology) ;
  • Song, Yeon-Jung (Institute of Bioscience & Biotechnology, Daewoong Pharm Co. LTD) ;
  • Seo, Kyung-Won (Department of Drug Evaluation, Korea Food and Drug Administration)
  • Published : 2004.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

The purpose of this study is to evaluate the effect of cigarette smoke condensate (CSC) on toxification/detoxification metabolic pathway in primary cultured rat hepatocytes. We measured the activities of cytochrome P450 monooxygenases (CYP450s) and UDP-glucuronyltransferase, sulfotransferase and glutathione-S-transferase in CSC-treated rat hepatocytes. CSC significantly increased the activities of hepatic CYP4501A1 and CYP4501A2 to 7.5 fold and 1.6 fold respectively, compared with control level. However, CSC did not affect the activities of conjugation enzymes. We a1so examined if treatment of CSC could change thc cytotoxicity of acetaminophen (AA) through modulation of metabolizing enzymes. In rat hepatocytes, pretreatment with CSC potentiated the cytotoxicity of AA. This result indicates that potentiation of AA toxicity by CSC pretreatment may be related to induction of CYP4501A1 and CYP4501A2.

Keywords

References

  1. Berry, M.N. and Friend, D.S. (1969) High-yield preparation of isolated rat liver parenchymal cells. A biochemical and fine structure study. Journal of Cell Biology 43, 506-520 https://doi.org/10.1083/jcb.43.3.506
  2. Blot, W.J., McLaughlin, J.K., Winn, D.M., Austin, D.F, Freenberg, R.S., Preston-Martin, S., Bernstein, L., Schoenberg, J.B., Sternhagen, A. and Fraumeni, J.F.Jr. (1988) Smoking and . drinking in relation to oral and pharyngeal cancer. Cancer Research 48, 3282-3287
  3. Boyd, E.M. and Bereezky, G.M. (1966) Liver necrosis from paracetamol. British Journal of Pharmacology 26, 606-614
  4. Burke, M.D. and Mayer, R.T. (1974). Direct fluorometric assay of a microsomal -dealkylation which is preferentially inducible by 3-methylcholanthrene. Drug Metabolism and Disposition 2, 583-588.
  5. Dahlin, D.C., Miwa, G.T., Lu, A.Y.H. and Nelson, S.D. (1984) Nacetyl- p-benzoquinoneimine; A cytochrome P450-mediated oxidation product of acetaminophen. Proceedings of the National Academy of Sciences, 81, 1327-1331 https://doi.org/10.1073/pnas.81.5.1327
  6. Fabre, I., Fabra, G., Marel, P., Bertaultperes, P. and Cano, J.P. (1988) Metabolism of cyclosporin A III. Interaction of microlide antibiotic, erythromycin, using rabbit hepatocytes and microsomal fractions, Drug Metabolism and Disposition 16, 296-301
  7. Habig, W.H., Pabst, M.J. and Jakoby, W.B. (1974). Glutathion Stransferase: the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry 249, 7130-7139
  8. Harvison, P.J., Guengerich, E.P., Rashed, M.S. and Nelaon, S.D. (1988) Cytochrome P450 isozymes selectivity in the oxidation of acetaminophen. Chemical Research in Toxicology, 1, 47-52 https://doi.org/10.1021/tx00001a009
  9. Hecht, S.S., Thome, R.L., Maronpot, R.R and Hoffmann, D. (1975) A Study of tobacco carcinogenesis. XIII. Tumor-promoting subfractions of the weakly acidic fraction. Journal of National Cancer Institute 55, 1329-1336 https://doi.org/10.1093/jnci/55.6.1329
  10. Hinson, J.A. (1982) cc. In Reviews in Biochemical Toxicology Edited by E. Hodgson, J.R. Bend, and R.M. Philpot, pp. 103-129. Elsevier/North-Holland, New York
  11. Hoffmann, D, and Wynder, E.L. (1971) A study of tobacco carcinogenesis. Tumor initators, tumor accelerators, and tumor promoting activity of condensate fractions. Cancer 27, 848-864 https://doi.org/10.1002/1097-0142(197104)27:4<848::AID-CNCR2820270415>3.0.CO;2-4
  12. Isselbacher, K.J., Chrabas, M.F. and Quinn, R.C. (1962) The solubilization and partial purification of a glucuroyl transferase from rabbit liver microsomes. Journal of Biological Chemistry 237, 3033-3030
  13. Kaul, K.L. and Novak, R.F. (1987) Inhibition and induction of rabbit liver microsomal cytochrome P-450 by pyridine. Journal of Pharmacology and Experimental Therapeutics 243, 384-390
  14. Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.T. (1951) Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 193, 265-275
  15. Lubet, R.A, Mayer, R.T., Cameron, J.W, Nims, R.W, Burke, M.D., Wolff, T. and Guengerich, E.P. (1985) Dealkylation of pentoxyresorufin : a rapid and sensitive assay for measuring induction of cytochrome(s)-p-450 by phenobarbital and other xenobiotics the rat. Archives of Biochemical Biophysics 238, 43-48 https://doi.org/10.1016/0003-9861(85)90138-9
  16. Mitchell, J.R., Jollow, D.J., Ptter, W.Z., Gillette, J.R. and Brodie, B.B. (1973) Acetaminophen-induced hepatic necrosis. IV. P.rotective role of glutathione. Journal of Pharmacology and Experimental Therapeutics 187, 211-217
  17. Nerukar, P.Y., Park, S.S., Thomas, P.E. and Lubet, R.A. (1993). Methoxyresorufin-a specific substrate for O-dealkylation by cytochrome P4501A2, Proceedings of the American Association for Cancer Reseach 34, 156
  18. Sekura, R.D. and Jakoby, W.B. (1979) Phenol sulfotransferases. Journal Biological Chemmistry 254, 5658-5662
  19. Tu, Y.Y. and Yang, C.S. (1983) High-affinity nitrosoamine dealkylase system in rat liver microsomes and its induction by fasting. Cancer Research 43, 623-629
  20. Van Duuren, B.L., Sivak, A., Katz, C. and Melchionne, S. (1971) Cigarette smoke carcinogenesis: Importance of tumor promoters. Journal of National Cancer Institute 47, 235-240
  21. Wynder, E.L. and Hoffmann, D. (1967) Tobacco and tobacco smoke, Studies in experimental carcinogenesis. New York, N.Y. Academic Press, Inc
  22. Wynder, E.L. and Hoffmann, D. (1968) Experimental tobacco carcinogenesis. Science 162, 862-871 https://doi.org/10.1126/science.162.3856.862