Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Initiation and promotion in hepatocarcinogenesis

  • 26 Accesses

  • 25 Citations


Initiation and promotion have been recognized as essential parts of the multi-stage concept of chemical carcinogenesis. In the liver, initiation by genotoxic carcinogens results in appearance of foci of phenotypically altered hepatocytes. Accelerated growth and phenotypic changes of these foci during tumor promotion by phenobarbital are described, and possible mechanisms of initiation and promotion considered.

This is a preview of subscription content, log in to check access.


  1. Bannasch P, Moore MA, Klimek F, Zerban H (1982) Biological markers of preneoplastic foci and neoplastic nodules in rodent liver. Toxicol Pathol 10: 19–36

  2. Bannasch P, Hacker HJ, Klimek F, Mayer D (1984) Hepatocellular glycogenesis and related pattern of enzymatic changes during hepatocarcinogenesis. In: Weber G (ed) Advances in enzyme regulation. Vol 22. Pergamon Press, Oxford New York

  3. Boutwell RK (1974) The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol 2: 419–443

  4. Bursch W, Lauer B, Timmermann-Trosiener I, Barthel G, Schuppler J, Schuhe-Hermann R (1984) Controlled death (apoptosis) of normal and putative preneoplastic cells in rat liver following withdrawal of tumor promoters. Carcinogenesis 5: 453–458

  5. Farber E, Cameron R (1980) The sequential analysis of cancer development. Adv Cancer Res 31: 125–225

  6. Hecker E (1978) Co-carcinogene oder bedingt krebsauslösende Faktoren. Aktuelle neue Aspekte der Ätiologie menschlicher Tumoren und des molekularen Mechanismus der Krebsentstehung. Naturwissenschaften 65: 640–648

  7. Klein G, Klein E (1985) Evolution to tumours and the impact of molecular oncology. Nature 315: 190–195

  8. Pitot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605: 191–215

  9. Reinacher M, Eigenbrodt E, Gerbracht U, Zenk G, Timmer mann-Trosiener I, Bentley P, Waechter F, Schoner W, Schulte-Hermann R (1986) Pyruvate kinase isoenzymes in altered foci and carcinoma of rat liver. Carcinogenesis 7: 1351–1357

  10. Remmer H, Merker HJ (1963) Drug-induced changes in the liver endoplasmic reticulum: association with drug-metabolizing enzymes. Science 142: 1657–1658

  11. Rutenberg AM, Kim H, Fischbein J, Hauker JS, Wasserkrug HC, Seligman R (1968) Histochemical and ultrastructural demonstration of γ-glutamyl transpeptidase activity. J Histochem Cytochem 17: 517–526

  12. Schulte-Hermann R (1974) Induction of liver growth by xenobiotic compounds and other stimuli. Crit Rev Toxicol 3: 97–158

  13. Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1982) Response of liver foci in rats to hepatic tumor promoters. Toxicol Pathol 10: 63–70

  14. Schulte-Hermann R, Roome N, Timmermann-Trosiener I, Schuppler J (1984a) Immunocytochemical demonstration of a phenobarbital-inducible cytochrome P450 in putative preneoplastic foci of rat liver. Carcinogenesis 5: 149–153

  15. Schulte-Hermann R, Timmermann-Trosiener I, Schuppler J (1984b) Aberrant expression of adaption to phenobarbital may cause selective growth of foci of altered cells in rat liver. In: Börzsony M, Lapis K, Day NE, Yamasaki H (eds) Models, mechanisms and etiology of tumor promotion. IARC Scientific Publication, Vol 56, pp 67–75

  16. Schulte-HermannR (1985) Tumor promotion in the liver. Arch Toxicol 57: 147–158

  17. Stäubli W, Bentley P, Bieri F, Fröhlich E, Waechter F (1984) Inhibitory effect of nafenopin upon the development of diethylnitrosamine-induced enzyme-altered foci within the rat liver. Carcinogenesis 5: 41–47

  18. Zarbl H, Sukumar S, Arthur AV, Martin-Zanca D, Barbacid M (1985) Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature 315: 382–385

Download references

Author information

Correspondence to R. Schulte-Hermann.

Additional information

Dedicated to Professor Dr. med. Herbert Remmer on the occasion of his 65th birthday

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schulte-Hermann, R. Initiation and promotion in hepatocarcinogenesis. Arch Toxicol 60, 179–181 (1987). https://doi.org/10.1007/BF00296976

Download citation

Key words

  • Hepatocarcinogenesis
  • Genotoxic carcinogens