Induction of rat liver glutathione transferase isoenzyme 7-7 by lead nitrate

  • Lennart Dock
Section 4 Mechanisms of Metal Toxicity


The glutathione transferase (GST) activity of rat liver cytosolic preparations with ethacrynic acid (EA) and (±)-7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydro-benzo(a)pyrene (BPDE) as substrates, increased by 125 and 350%, respectively, in animals that had been treated with a single intravenous dose of Pb(NO3)2 (100 μmol/kg body wt) 48 h prior to sacrifice, whereas activity with 1-chloro-2,4-dinitro-benzene (CDNB) increased only about 60%. No induction of these activities was observed in cytosolic preparations from regenerating rat liver, whereas cytosols prepared from hepatocyte nodules showed increased activity with all three substrates (EA: 400%; BPDE: 790%; CDNB: 205%).

These results suggest that Pb(NO3)2 is an inducer of GST 7-7, an isoenzyme that has been associated with hepatocarcinogenesis. Elucidation of the mechanism of GST 7-7 induction by lead may contribute to our understanding of the process of chemical carcinogenesis.

Index Entries

Glutathione transferase induction lead diolepoxide carcinogenesis liver 


  1. 1.
    M. W. Roomi, A. Columbano, G. M. Ledda-Columbano, and D. S. R. Sarma,Carcinogenesis 7, 1643 (1986).PubMedCrossRefGoogle Scholar
  2. 2.
    A. Columbano, M. Ledda-Columbano, P. Sirigu, T. Perra, and P. Pani,Am. J. Pathol. 110, 83 (1983).PubMedGoogle Scholar
  3. 3.
    E. Farber and D. S. R. Sarma,Lab. Invest. 56, 4 (1987).PubMedGoogle Scholar
  4. 4.
    K. Sato, A. Kitahara, K. Satoh, T. Ishikawa, M. Tatematsu, and N. Ito,Gann 75, 199 (1984).PubMedGoogle Scholar
  5. 5.
    H. Jensson, L. C. Eriksson, and B. Mannervik,FEBS Lett. 187, 115 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    S. E. H. Russell, C. Pearson, M. Kelly, S. McQuaid, and P. Humphries,Biochem. J. 249, 105 (1988).PubMedGoogle Scholar
  7. 7.
    N. Ito, H. Tsuda, M. Tatematsu, T. Inoue, Y. Tagawa, T. Aoki, S. Uwagawa, M. Kagawa, T. Ogiso, T. Masui, K. Imaida, S. Fukushima, and M. Asamoto,Carcinogenesis 9, 387 (1988).PubMedCrossRefGoogle Scholar
  8. 8.
    B. Mannervik, P. Ålin, C. Guthenberg, H. Jensson, M. K. Tahir, M. Warholm, and H. Jörnvall,Proc. Natl. Acad. Sci. USA 82, 7202 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    T. C. Shea, S. L. Kelley, and W. D. Henner,Cancer Res. 48, 527 (1988).PubMedGoogle Scholar
  10. 10.
    Y. Shiraturi, Y. Soma, H. Maruyama, S. Sato, A. Takano, and K. Sato,Cancer Res. 47, 6806 (1987).Google Scholar
  11. 11.
    S. Hesse, B. Jernström, M. Martinez, P. Moldéus, L. Christodoulides, and B. Ketterer,Carcinogenesis 3, 757 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    D. J. Reed, J. R. Babson, P. W. Beatty, A. E. Brodie, W. W. Ellis, and D. W. Potter,Anal. Biochem. 16, 55 (1980).CrossRefGoogle Scholar
  13. 13.
    W. H. Habig and W. B. Jacoby,Meth. Enzymol. 77, 398 (1981).PubMedCrossRefGoogle Scholar
  14. 14.
    I. G. C. Robertson, H. Jensson, B. Mannervik, and B. Jernström,Carcinogenesis 7, 295 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    B. Jernström, I. G. C. Robertson, B. Mannervik, and L. Dock, F. Feo, P. Pani, A. Columbano, and R. Garcea, eds,Chemical Carcinogenesis, Plenum, 1988, pp. 67–73.Google Scholar
  16. 16.
    C. Power, S. Sinha, C. Webber, M. M. Manson, and G. E. Neal,Carcinogenesis 8, 797 (1987).PubMedCrossRefGoogle Scholar
  17. 17.
    A. Columbano, G. M. Ledda-Columbano, P. Coni, and P. Pani,Carcinogenesis 8, 345 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    Z. Gregus and C. D. Klaassen,Toxicol. Appl. Pharmacol. 85, 24 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    J. G. Pounds,Neurotoxicol. 5, 295 (1984).Google Scholar

Copyright information

© The Humana Press Inc. 1989

Authors and Affiliations

  • Lennart Dock
    • 1
  1. 1.Institute of Environmental MedicineKarolinska institutetStockholmSweden

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