Advertisement

Role of Parenchymal Versus Non-Parenchymal Cells on the Control of Biologically Reactive Intermediates

  • Franz Oesch
  • Mark Lafranconi
  • Hans-Ruedi Glatt
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

The non-parenchymal cells (NPC) of the liver have the potential to significantly influence the formation of reactive intermediates in the liver because of their critical location along the sinusoids where they are the first cells to encounter blood borne xenobiotics. To study the possible role of the NPC in the metabolism of xenobiotics, populations of NPC and parenchymal cells (PC) were prepared from rats and various xenobiotic metabolizing enzyme activities investigated. The specific activity of every enzyme studied was 12 to 1000% higher in the PC than in the NPC populations and the pattern of activities between the 2 populations was remarkably different. The NPC also displayed a more dramatic response to Aroclor 1254 induction of enzyme activities than did the PC. Furthermore, the NPC were capable of forming biologically reactive intermediates which caused cyto- and genotoxicity. From these data we conclude that the NPC provide a distinct contribution to hepatic metabolism of xenobiotics.

Keywords

Parenchymal Cell Reactive Intermediate Epoxide Hydrolase Mercapturic Acid Bacterial Mutagenicity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R. Daoust, Liver function, in: “American Institute Biological Sciences” publication # 4, R. W. Brauer, ed., pp. 3–10 (1958).Google Scholar
  2. 2.
    J. L. Creech Jr., and M. N. Johnson, Angiosarcoma of the liver in the manufacture of polyvinyl chloride, J. Occup. Med. 16: 150–151 (1974).PubMedGoogle Scholar
  3. 3.
    M. A. Bedell, J. G. Lewis, K. C. Billings, and J. A. Swenberg, Cell specificity in hepatocarcinogenesis: preferential accumulation of 06 methylguanine in target cell DNA during continuous exposure of rats to 1,2-dimethylhydrazine, Cancer Res., 42: 3079–3083 (1982).PubMedGoogle Scholar
  4. 4.
    H. Druckrey, “Organospecific carcinogenesis in the digestive tract”, in: Topics in Chemical Carcinogenesis, W. Nakahara, S. Takayama, T. Sugimura, and S. Odashima, eds., University Park Press, Tokyo, pp. 73–101 (1972).Google Scholar
  5. 5.
    E. Cantrell, and E. Bresnick, Benzpyrene hydroxylase activity in isolated parenchymal and nonparenchymal cells of rat liver, J. Cell Biol. 52: 316–321 (1972).PubMedCrossRefGoogle Scholar
  6. 6.
    J. Morland, and H. Olsen, Metabolism of sulfadimidine, sulfanilamide, para aminobenzoic acid, and isoniazid in suspensions of parenchymal and nonparechymal rat liver cells, Drug Metab. Disp. 5: 511–517 (1977).Google Scholar
  7. 7.
    D. J. McCaustland, and J. F. Engel, Metabolites of aromatic hydrocarbons. II. Synthesis of 7,8-dihydrobenzo[a]pyrene-7,8-diol and 7,8-dihydrobenzo[a]pyrene-7,8-epoxide, Tetrahedron Lett., 2059–2552 (1975).Google Scholar
  8. 8.
    P. P. Fu, and R. G. Harvey, Synthesis of the diols and the dioepoxides of carcinogenic hydrocarbons, Tetrahedron Lett., 2059–2062 (1977).Google Scholar
  9. 9.
    H. R. Glatt, R. Billings, K. L. Platt, and F. Oesch, Improvement of the correlation of bacterial mutagenicity with carcinogenicity of benzo[a]pyrene and four of its major metabolites by activation with intact liver cells instead of cell homogenate, Cancer Res. 41: 270–277 (1981).PubMedGoogle Scholar
  10. 10.
    D. M. Mills, and D. Zucker-Franklin, Electron microscopic study of isolated Kupffer cells. Am. J. Pathol. 54: 147–155 (1969).PubMedGoogle Scholar
  11. 11.
    J. A. Swenberg, M. A. Bedell, K. C. Billings, D. R. Umbenhauer, and A. Pegg, Cell specific differences in 06-alkylguanine DNA repair activity during continuous exposure to carcinogen, Proc. Natl. Acad. Sci. 79: 5499–5502 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    D. P. Praaning van Dalen, and D. L. Knook, Quantitative determinations of in vivo endocytosis by rat liver Kupffer and endothelial cells facilitated by an improved cell isolation method, FEBS Lett. 141: 229–232 (1982).CrossRefGoogle Scholar
  13. 13.
    D. L. Knook, and E. Ch. Sleyster, Isolated parechymal, Kupffer and endothelial rat liver cells characterized by their lysosomal enzyme content, Biochem. Biophys. Res. Comm. 96: 250–257 (1980).PubMedCrossRefGoogle Scholar
  14. 14.
    W. M. Lafranconi, H. R. Glatt, and F. Oesch, Xenobiotic metabolizing enzymes of rat liver non-parenchymal cells, manuscript in preparation.Google Scholar
  15. 15.
    D. L. Knook, and E. Ch. Sleyster, Separation of Kupffer and endothelial cells of the rat liver by centrifugal elutriation. Exp. Cell Res. 99: 444–449 (1976).PubMedCrossRefGoogle Scholar
  16. 16.
    T. J. J. van Berkel, J. F. Koster, and W. C. Hulsmann, Distribution of L and M type pyruvate kinase between parenchymal and Kupffer cells of rat liver, Biochim. Biophys. Acta 276: 425–429 (1972).Google Scholar
  17. 17.
    H. U. Bergmeyer, and E. Bernt, in: Methoden der enzymatischen Analyse, H. U. Bergmeyer, ed., Verlag Chemie, Weinheim/Bergstraße, FRG, pp. 533–538 (1970).Google Scholar
  18. 18.
    T. Mossman, Rapid colorimetric assay for cellular growth and survival: Appliction to proliferation and cytotoxicity assays, J. Immunol. Methods 65: 55–63 (1983).CrossRefGoogle Scholar
  19. 19.
    A. Y. H. Lu, A. Somogyi, S. West, R. Kutzman, and H. H. Conney, Pregnenolone-16a-carbonitrile: A new type of inducer of drug metabolizing enzymes, Arch. Biochem. Biophys. 152: 457–462 (1972).PubMedCrossRefGoogle Scholar
  20. 20.
    M. D. Burke, and R. T. Mayer, Ethoxyresurofin: Direct fluorimetric assay of a microsomal 0-dealkylation which is preferentially inducible by 3-methylcholanthrene, Drug Metab. Disp. 2: 583–588 (1974).Google Scholar
  21. 21.
    T. Omura, and R. Sato, The carbon monooxide binding pigment of liver microsomes. J. Biol. Chem. 239: 2370–2378 (1964).PubMedGoogle Scholar
  22. 22.
    H. U. Schmassmann, H. R. Glatt, and F. Desch, A rapid assay for epoxide hydratase activity with benzo[a]pyrene 4,5-(K-region)oxide as substrate, Anal. Biochem. 74: 94–104 (1976).Google Scholar
  23. 23.
    W. H. Habig, M. J. Pabst, and W. B. Jakoby, Glutathione transferases: The first step in mercapturic acid formation, J. Biol. Chem. 249: 7130–7139 (1974).PubMedGoogle Scholar
  24. 24.
    K. W. Bock, B. Burchell, G. J. Dutton, O. Hanninen, G. J. Mulder, I. S. Owens, G. Sies, and T. R. Tephly, UDP-glucuronosyltransferase activities: Guidelines for consistent interim terminology and assay conditions, Biochem. Pharmacol. 32: 953–955 (1983).PubMedCrossRefGoogle Scholar
  25. 25.
    O. H. Lowry, J. Rosebrough, A. L. Farr, and R. J. Randall, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193: 265–275 (1951).PubMedGoogle Scholar
  26. 26.
    C. W. Dunnett, New tables for multiple comparisons with a control Biometrics 6: 482–494 (1964).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Franz Oesch
    • 1
  • Mark Lafranconi
    • 1
  • Hans-Ruedi Glatt
    • 1
  1. 1.Institut für ToxikologieUniversität MainzMainzGermany

Personalised recommendations