Minimal Neoplasias in Experimental Liver Carcinogenesis

  • H. M. Rabes
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 106)

Abstract

The rodent liver provides a unique opportunity to study the early stages of chemical carcinogenesis. If a rat or a mouse is exposed for a long period to a hepatocarcinogen, hepatocellular carcinomas develop which invade and replace part of the normal liver, and sometimes tumor cells disseminate to give rise to lung metastasis. Long before this final stage is reached cellular changes can be observed in the liver parenchyma. Foci of altered hepatocytes appear which show an aberration from the enzymatic pattern of normal hepatocytes. These foci can best be demonstrated in enzyme histochemical preparations in cryostat sections prepared from the liver at early stages of carcinogen exposure. Small islands of hepatocytes are then seen which show a deficiency of glucose-6-phosphatase as described in a preliminary report first in 1964 by the Friedrich-Freksa group (Gössner and Friedrich-Freksa 1964). In the same year, Bannasch and Müller reported that during hepatocarcinogenesis foci of glycogen-storing cells can be observed and they related their occurrence to the previous exposure to a hepatocarcinogen. Interestingly, it was in 1961 that Grundmann pointed out that basophilic foci occur in the liver after carcinogen exposure and he suggested that these subpopulations in the liver might represent precursor lesions in hepatocarcinogenesis.

Keywords

Hydrocortisone Hydrolase Phenobarbital Pentose Transferase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bannasch P (1986) Preneoplastic lesions as end points in carcinogenicity testing: I. Hepatic preneoplasia. Carcinogenesis 7: 689–695PubMedCrossRefGoogle Scholar
  2. Bannasch P, Müller HA (1964) Lichtmikroskopische Untersuchungen über die Wirkung von NNitrosomorpholin auf die Leber von Ratte und Maus. Arzneimittelforsch 14: 805–814PubMedGoogle Scholar
  3. Bannasch P, Mayer D, Hacker HJ (1980) Hepatocellular glycogenosis and hepatocarcinogenesis. Biochim Biophys Acta 605: 217–245PubMedGoogle Scholar
  4. Craddock VM (1976) Cell proliferation and experimental liver cancer. In: Cameron D, Linsell A, Warwick GP (eds) Liver cell cancer. Elsevier, Amsterdam, pp 153–201Google Scholar
  5. Farber E (1980) The sequential analysis of liver cancer induction. Biochim Biophys Acta 605: 149–166PubMedGoogle Scholar
  6. Gössner W, Friedrich-Freksa H (1964) Histochemische Untersuchungen über die Glucose-6-Phosphatase in der Rattenleber während der Cancerisierung durch Nitrosamine. Z Naturforsch [B] 19: 862–864Google Scholar
  7. Grundmann E (1961) Die Zytogenese des Krebses. Dtsch Med Wochenschr 86: 1077–1084PubMedCrossRefGoogle Scholar
  8. Holecek B, Rabes HM (1986) Cytogenetic analyses of normal and diethylnitrosamine-initiated preneoplastic hepatocytes. J Cancer Res Clin Oncol 111: S95CrossRefGoogle Scholar
  9. Howell S, Wareham KA, Williams ED (1985) Clonal origin of mouse liver cell tumors. Am J Pathol 121: 426–432PubMedGoogle Scholar
  10. Kaufmann WK, Kaufman DG, Rice JM, Wenk ML (1981) Reversible inhibition of rat hepatocyte proliferation by hydrocortisone and its effect on cell cycle-dependent hepatocarcinogenesis by N-methyl-N-nitrosourea. Cancer Res 41: 4653–4660PubMedGoogle Scholar
  11. Kaufmann WK, Mackenzie SA, Kaufman DG (1985) Quantitative relationship between hepatocytic neoplasms and islands of cellular alteration during hepatocarcinogenesis in male F344 rat. Am J Pathol 119: 171–174PubMedGoogle Scholar
  12. Kerler R, Rabes HM (1986) In vitro propagation of preneoplastic hepatocytes initiated in vivo by diethylnitrosamine. J Cancer Res Clin Oncol 111: S46CrossRefGoogle Scholar
  13. Kunz W, Appel KE, Rickart R, Schwarz M, Stöckle G (1978) Enhancement and inhibition of carcinogenic effectiveness of nitrosamines. In: Remmer H, Bolt HM, Bannasch P, Popper H (eds) Primary liver tumors. MTP Press, Lancaster, pp 261–283Google Scholar
  14. Maguire S, Rabes HM (1987) Transformation sensitivity in early S-phase and clonogenic potential are target-cell characteristics in liver carcinogenesis by N-methyl-N-nitrosourea. Int J Cancer 39: 385–389PubMedCrossRefGoogle Scholar
  15. Nowell PC (1976) The clonal evolution of tumour cell populations. Science 194: 23–28PubMedCrossRefGoogle Scholar
  16. Pitot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605: 191–215PubMedGoogle Scholar
  17. Rabes HM (1983) Development and growth of early preneoplastic lesions induced in the liver by chemical carcinogens. J Cancer Res Clin Oncol 106: 85–92PubMedCrossRefGoogle Scholar
  18. Rabes HM, Szymkowiak W (1979) Cell kinetics of hepatocytes during the preneoplastic period of diethylnitrosamine-induced liver carcinogenesis. Cancer Res 39: 1298–1304PubMedGoogle Scholar
  19. Rabes HM, Kerler R, Wilhelm R, Rode G, Riess H (1979) Alkylation of DNA and RNA by (14C) dimethylnitrosamine in hydroxyurea-synchronized regenerating rat liver. Cancer Res 39: 4228–4236PubMedGoogle Scholar
  20. Rabes HM, Bücher T, Hartmann A, Linke I, Dünnwald M (1982a) Clonal growth of carcinogen-induced enzyme-deficient preneoplastic cell populations in mouse liver. Cancer Res 42: 3220–3227PubMedGoogle Scholar
  21. Rabes HM, Wilhelm K, Kerler R, Rode G (1982b) Dose-and cell cycle-dependent O6-methylguanine elimination from DNA in regenerating rat liver after (14C)dimethylnitrosamine injection. Cancer Res 42: 3814–3821PubMedGoogle Scholar
  22. Rabes HM, Kerler R, Rode G, Schuster C, Wilhelm R (1984) O6-Methylguanine repair in liver cells in vivo: comparison between G1- and S-phase of the cell cycle. J Cancer Res Clin Oncol 108: 36–45PubMedCrossRefGoogle Scholar
  23. Rabes HM, Müller L, Hartmann A, Kerler R, Schuster CH (1986) Cell-cycle dependent initiation of ATPase-deficient populations in adult rat liver by a single dose of N-methyl-N-nitrosourea. Cancer Res 46: 645–650PubMedGoogle Scholar
  24. Sarafoff, Rabes HM, Dörmer P (1986) Correlations between ploidy and initiation probability determined by DNA cytophotometry in individual altered hepatic foci. Carcinogenesis 7: 1191–1196PubMedCrossRefGoogle Scholar
  25. Scherer E (1984) Neoplastic progression in experimental hepatocarcinogenesis. Biochim Biophys Acta 738: 219–236PubMedGoogle Scholar
  26. Schulte-Hermann R, Ohde G, Schuppler J, Timmermann-Trosiener I (1981) Enhanced proliferation of putative preneoplastic cells in rat liver following treatment with the tumor promoters phenobarbital, hexachlorocyclohexane, steroid compounds and nafenopin. Cancer Res 41: 2556–2562PubMedGoogle Scholar
  27. Schuster C, Rode G, Rabes HM (1985) O6-Methylguanine repair of methylated DNA in vitro: cell cycle-dependence of rat liver methyltransferase activity. J Cancer Res Clin Oncol 110: 98–102PubMedCrossRefGoogle Scholar
  28. Solt D, Farber E (1976) New principle for the analysis of chemical carcinogenesis. Nature 263: 702–703CrossRefGoogle Scholar
  29. Vesselinovitch SD, Koka M, Mihailovich N, Rao KVN (1984) Carcinogenicity of diethylnitrosamine in newborn, infant and adult mice. J Cancer Res Clin Oncol 108: 60–65PubMedCrossRefGoogle Scholar
  30. Warwick GP (1971) Effect of the cell cycle on carcinogenesis. Fed Proc 30: 1760–1765PubMedGoogle Scholar
  31. Williams GM (1980) The pathogenesis of rat liver cancer caused by chemical carcinogens. Biochim Biophys Acta 605: 167–189PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1988

Authors and Affiliations

  • H. M. Rabes
    • 1
  1. 1.Pathologisches InstitutUniversität MünchenMünchen 2Germany

Personalised recommendations