Covalent Binding of CCl4-Intermediates to Reduced Pyridine Nucleotides in Mouse Liver

  • D. Kitta
  • M. Schwarz
  • H. A. Tennekes
  • H. Uehleke
  • W. Kunz
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Carbontetrachloride (CCl4) is hepatotoxic and has also been shown to produce liver tumours in several rodent species (Andervont, 1958; Edwars, 1941; Edwars and Dalton, 1942; Edwars et al., 1942; Reuber, 1970; Reuber and Gloves, 1970). It is virtually certain that these effects are due to the generation of reactive intermediates from the parent compound in liver microsomes. CC14-inter-mediates have been shown to bind irreversibly to hepatocellular proteins and lipids (Reynolds, 1967; Recknagel, 1967), the latter effect leading to lipid peroxidation (Glende, 1972).

Keywords

Chlorine Pyridine Adduct NADPH NADH 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andervont, H.B., 1958, Induction of hepatomas in strain C3H mice with 4–0-tolyazo-0-toluidine and carbon tetrachloride, J. Natl. Cancer Inst. 20:431.Google Scholar
  2. Diaz Gomez, M.J. and Castro, J.A., 1978, Covalent binding of carbon tetrachloride metabolites to liver nuclear DNA, proteins, and lipids, Toxicol. Appl. Pharmacol. 45:315.Google Scholar
  3. Edwars, J.E., 1941, Hepatomas in mice induced with carbon tetrachloride, J. Natl. Cancer Inst. 2: 197.Google Scholar
  4. Edwars, J.E. and Dalton, A.J., 1942, Induction of cirrhosis of the liver and of hepatomas in mice with carbon tetrachloride, J. Natl. Cancer Inst. 3:19.Google Scholar
  5. Edwars, J.E., Heston, W.E. and Dalton, A.J., 1942, Induction of carbon tetrachloride hepatomas in strain L mice, J. Natl. Cancer Inst. 3:297.Google Scholar
  6. Glende, E.A., 1972, On the mechanism of carbon tetrachloride toxicity-coincidence of loss of drug-metabolizing activity with per-oxidation of microsomal lipid. Biochem. Pharmacol. 21:2131.Google Scholar
  7. Kaplan, N.O., 1960, The pyridine coenzymes, in: “The enzymes”, Boyes, P.D., Lardy, H. and Myrbäck, K., eds., Academic Press, N.Y. and London, 3: 105.Google Scholar
  8. Oppenheimer, N.J. and Kaplan, N.O., 1974, Structure of the primary acid rearrangement product of reduced nicotinamide adenine dinucleotide (NADH), Biochemistry 13: 4681.Google Scholar
  9. Pullman, B. and Pullman, A., 1959, The electronic structure of the respiratory coenzymes, Proc. Nat. Acad. Sci. USA 45:136.Google Scholar
  10. Recknagel, R.O., 1967, Carbon tetrachloride hepatotoxicity, Pharmacol. Rev. 19:145.Google Scholar
  11. Reuber, M.D., 1970, Effect of 3-methylcholanthrene on hyperplastic and early neoplastic hepatic lesions induced in rats by carbontetrachloride, J. Natl. Cancer Inst. 45:1237.Google Scholar
  12. Reuber, M.D. and Glover, E.L., 1970, Cirrhosis and carcinoma in the liver in male rats given subcutaneous carbon tetrachloride, J. nat. Cancer Inst. 44: 419.Google Scholar
  13. Reynolds, E.S., 1967, Liver parenchymal cell injury. IV. Pattern of incorporation of carbon and chlorine from carbon tetrachloride into chemical constituents of liver in vivo, J. Pharmacol. exp. Ther. 155:117.Google Scholar
  14. Rocchi, P., Prodi, G., Grilli, S. and Ferreri, A.M., 1973, in vivo and in vitro binding of carbon tetrachloride with nucleic acids and proteins in rat and mouse liver, Int. J. Cancer 11:419.Google Scholar
  15. Schwarz, M., Hummel, J., Appel, K.E., Rickart, R. and Kunz, W., 1979, DNA Damage induced in vivo evaluated with a nonradioactive alkaline elution technique, Cancer Letters 6:221.Google Scholar
  16. Uehleke, H. and Werner, Th., 1975, A comparative study on the irreversible binding of labelled halothane, trichlorofluoromethane, chloroform, and carbon tetrachloride to hapatic protein and lipids in vitro and in vivo, Arch. Toxicol. 34:289.Google Scholar
  17. Yoshida, A. and Dave, V., 1975, Inhibition of NADP-dependent dehydrogenases by modified products of NADPH, Arch. Biochem.Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • D. Kitta
    • 1
  • M. Schwarz
    • 1
  • H. A. Tennekes
    • 1
  • H. Uehleke
    • 1
    • 2
  • W. Kunz
    • 1
  1. 1.Institute of BiochemistryThe German Cancer Research CentreHeidelbergGermany
  2. 2.Dept. of ToxicologyBundesgesundheitsamtBerlin (West) 33Germany

Personalised recommendations