• Hans-Günther Neuman


According to a recent worldwide survey, liver cancer ranks seventh among tumors in males and ninth in females.1 Only a few agents have so far been associated more directly with the development of these tumors in man. Among them are: aflatoxins, cycasin, vinyl chloride, and estrogens, agents of quite different chemical nature. In experimental animals, mostly the rat and the mouse, quite a number of diverse chemicals have been demonstrated to produce liver tumors. Accordingly, such chemicals are called hepatocarcinogens.


Liver Tumor Aromatic Amine Partial Hepatectomy Oxidize Glutathione Unilateral Nephrectomy 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    D. M. Parkin, J. Stjernward, and C. S. Muirs, Estimates of cancer occurrance throughout the world. International Agency for Research on Cancer, Lyon, France (1986).Google Scholar
  2. 2.
    P. Bannasch and H. A. Müller, Lichtmikroskopische Untersuchungen über die Wirkung von N-Nitrosomorpholin auf die Leber von Ratte und Maus, Arzneim. Forsch., 14:805 (1964).Google Scholar
  3. 3.
    P. Bannasch, U. Brenner., H. Enzmann, and H. J. Hacker, Tigroid cell foci and neoplastic nodules in the liver of rats treated with a single dose of aflatoxin B1, Carcinogenesis 6: 1641 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    H. C. Pitot and A. E. Sirica, The stages of initiation and promotion in hepatocarcinogenesis, Biochim. Biophys. Acta 605: 191 (1980).PubMedGoogle Scholar
  5. 5.
    O. H. Iversen and E. G. Astrup, The paradigm of two-stage carcinogenesis: a critical attitude, Cancer Investig. 2: 51 (1984).CrossRefGoogle Scholar
  6. 6.
    C. Peraino, R. J. M. Fry, E. Staffeldt, and J. P. Christopher, Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyl-trichloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat, Cancer Res. 35:2884 (1975).PubMedGoogle Scholar
  7. 7.
    H.-G. Neumann, the role of DNA damage in chemical carcinogenesis of aromatic amines, J. Cancer Res. Clin. Oncol. 112: 100 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    F. F. Kadlubar and F. A. Beland, Chemical properties of ultimate carcinogenic metabolites of arylamines and arylamides, in: R. G. Harvey, ed., Polycyclic Hydrocarbons and Carcinogenesis, ACS Symposium Series, No. 283, American Chemical Society, Washington (1985), pp 341.CrossRefGoogle Scholar
  9. 9.
    M. Ruthsatz, R. Franz, and H.-G. Neumann, DNA-damage, initiation and promotion by aromatic amines, in: Primary changes and control factors in carcinogenesis, T. Friedberg and F. Oesch, ed., Deutscher Fachschriften-Verlag, Wiesbaden (1986).Google Scholar
  10. 10.
    R. Franz, H.-R. Schulten, and H.-G. Neumann, Identification of nucleic acid adducts from trans-4-acetylaminostilbene, Chem.-Biol. Interactions 59: 281 (1986).CrossRefGoogle Scholar
  11. 11.
    R. Franz and H.-G. Neumann, Reaction of trans-4-N-acetoxy-N-acetylaminostilbene with guanosine, deoxyguanosine, RNA and DNA in vitro: predominant product is a cyclic N2,N3-guanine adduct, Chem.-Biol. Interactions in press.Google Scholar
  12. 12.
    D. Hilpert, W. Romen, and H.-G. Neumann, The role of partial hepatectomy and of promoters in the formation of tumors in non-target tissues of trans-4-acetylaminostilbene in rats, Carcinogenesis 4: 1519 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    J. D. Scribner and G. Koponen, Binding of the carcinogen 2-acetamidophenanthrene to rat liver nucleic acids: lack of correlation with carcinogenic activity, and failure of the hydroxamic acid ester model for in vivo activation, Chem.-Biol. Interactions 28: 201 (1979).CrossRefGoogle Scholar
  14. 14.
    J. D. Scribner and N. K. Mottet, DDT acceleration of mammary gland tumors induced in the male Sprague-Dawley rat by 2-acetamidophenanthrene, Carcinogenesis 2: 1235 (1981).PubMedCrossRefGoogle Scholar
  15. 15.
    N. K. Scribner, K. S. Rector, and B. A. Woodworth, Relative orders of initiating potencies of four aromatic amides may be similar in target and in non-target tissues, Proc. Third Intern. Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds, Detroit (1987).Google Scholar
  16. 16.
    R. C. Gupta and N. R. Dighe, Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl, and 2-acetylaminophenanthrene, Carcinogenesis 5: 343 (1984).PubMedCrossRefGoogle Scholar
  17. 17.
    G. P. Warwick, The covalent binding of metabolites of tritiated 2-methyl-4-dimethylaminoazobenzene to rat liver nucleic acids and proteins, and the carcinogenicity of the unlabeled compound in partially hepatectomized rats, Eur. J. Cancer 3: 227 (1967).PubMedGoogle Scholar
  18. 18.
    T. Kitagawa, H. C. Pitot, E. C. Miller, and J. A. Miller, Promotion by dietary phenobarbital of hepatocarcinogenesis by 2-methyl-N,N-dimethyl-4-aminoazobenzene in the rat, Cancer Res. 39: 112 (1979).PubMedGoogle Scholar
  19. 19.
    R. Daoust, Toxic effects of 2-methyl-4-dimethylaminoazobenzene in normal and partially hepatectomized rats, Chem.-Biol. Interactions 48: 221 (1984).CrossRefGoogle Scholar
  20. 20.
    R. Schulte-Hermann, Tumor promotion in the liver, Arch. Toxicol. 57: 147 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    E. Farber and R. Cameron, The sequential analysis of cancer development, Adv. Cancer Res. 31: 125 (1980).PubMedCrossRefGoogle Scholar
  22. 22.
    A. K. Laird and A. D. Barton, Cell growth and the development of tumours, Nature (London) 183: 1655 (1959).CrossRefGoogle Scholar
  23. 23.
    J. C. Arcos and M. F. Argus, Chemical Induction of Cancer, Vol. II B, Academic Press, London (1974), pp 49.Google Scholar
  24. 24.
    B. Flaks, Changes in the fine structure of rat hepatocytes during the early phases of chronic 2-acetylaminofluorene intoxication, Chem.-Biol. Interactions 2: 129 (1970).CrossRefGoogle Scholar
  25. 25.
    R. E. Albert, F. J. Burns, L. Bilger, D. Gardner, and W. Troll, Cell loss and proliferation induced by N-2-fluorenylacetamide in the rat liver in relation to hepatoma induction, Cancer Res. 32: 2172 (1972).PubMedGoogle Scholar
  26. 26.
    P. Marquardt, W. Romen, and H.-G. Neumann, Tissue specific acute toxic effects of the carcinogen trans-4-dimethylaminostilbene, Arch. Toxicol. 56: 151 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    A. Pfeifer and H.-G. Neumann, Organ specific acute toxicity of the carcinogen trans-4-acetylaminostilbene is not correlated with macromolecular binding, Chem.-Biol. Interactions 59: 185 (1986).CrossRefGoogle Scholar
  28. 28.
    A. Stier, R. Clauss, A. Lücke, and I. Reitz, Radicals in carcinogenesis by aromatic amines, in: D. C. H. McBrien and T. F. Slater, eds.. Free radicals, lipid peroxidation and cancer, Academic Press, London, New York (1982).Google Scholar
  29. 29.
    C. V. Smith and J. R. Mitchell, Acetaminophen hepatotoxicity invivo is not accompanied by oxidant stress, Biochim. Biophys. Res. Commun. 133: 329 (1985).CrossRefGoogle Scholar
  30. 30.
    J. Kuchlbauer, W. Romen, and H.-G. Neumann, Syncarcinogenic effects on the initiation of rat liver tumors by trans-4-acetylaminostilbene and 2-acetylaminofluorene, Carcinogenesis 6: 1337 (1985).PubMedCrossRefGoogle Scholar
  31. 31.
    P. Cikryt, Cytosolic binding proteins for aromatic hydrocarbons and their affinity for aromatic amines, in: T. Friedberg and F. Oesch, eds.. Primary changes and control factors in carcinogenesis, Deutscher Fachschriften-Verlag, Wiesbaden (1986).Google Scholar
  32. 32.
    M. Göttlicher and P. Cikryt, Induction of the aromatic hydrocarbon receptor and of drug metabolizing enzymes by various aromatic amines in rat liver, Naunyn Schmiedeberg’s Arch. Pharmacol. 335:R8 Suppl. (1987).CrossRefGoogle Scholar
  33. 33.
    H.-G. Neumann, The metabolism of repeatedly administered trans-4-dimethylaminostilbene and 4-dimethylaminobibenzyl, Z. Krebsforsch. 79: 60 (1973).CrossRefGoogle Scholar
  34. 34.
    A. Aström and J. W. DePierre, Characterization of the induction of drug metabolizing enzymes by 2-acetylaminofluorene, Biochim. Biophys. Acta 673: 225 (1981).PubMedGoogle Scholar
  35. 35.
    D. W. Nebert, N. M. Jensen, J. W. Perry, and T. Oka, Association between ornithine decarboxylase induction and the Ah locus in mice treated with polycyclic aromatic compounds, J. Biol. Chem. 255: 6836 (1980).PubMedGoogle Scholar
  36. 36.
    M. Göttlicher and P. Cikryt, Induction of ornithine decarboxylase by aromatic amines in rat liver, Cancer Letters 35: 65 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Hans-Günther Neuman
    • 1
  1. 1.Institute of Pharmacology and ToxicologyUniversity of WürzburgGermany

Personalised recommendations