Skip to main content
Log in

Morphometric study of alterations of extrafocal hepatocytes of rat liver treated with N-Nitrosomorpholine

  • Published:
Virchows Archiv B

Summary

Male Sprague-Dawley rats were treated with the hepatocarcinogen N-nitrosomorpholine for 7 weeks and observed for up to 40 weeks after withdrawal of the carcinogen. In addition to the focal preneoplastic lesions described earlier there were also alterations in extrafocal hepatocytes and these changes have been quantified morphometrically. Since the periportal and perivenous hepatocytes were not altered to the same extent, cells of the periportal zone (PPZ) and cells of the perivenous zone (PVZ) were measured separately. Immediately after stopping treatment there was marked enlargement of the hepatocellular cytoplasm and of the nuclei in both the PPZ and the PVZ and a reduction in the number of binuclear hepatocytes. While these alterations were totally reversed during the first 10 weeks after treatment ceased in the PPZ, statistically significant changes in nuclear size, nuclear-cytoplasmic ratio and number of binuclear cells persisted in the PVZ up to 40 weeks after the end of treatment. We suggest that both the foci of altered hepatocytes as well as the persisting changes in extrafocal hepatocytes may be involved in the process of hepatocarcinogenesis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abmayr A, Deml E, Oesterle D, Goessner W (1983) Nuclear morphology in preneoplastic lesions of rat liver. Anal Quant Cytol 5:275–284

    PubMed  CAS  Google Scholar 

  • Bannasch P (1968) The cytoplasm of hepatocytes during carcinogenesis. Rec Res Cancer Res 19 Springer, Berlin Heidelberg New York

    Google Scholar 

  • Bannasch P (1986) Preneoplastic lesions as end points in carcinogenicity testing. I. Hepatic preneoplasia. Carcinogenesis 7:689–695

    Article  PubMed  CAS  Google Scholar 

  • Bannasch P, Papenburg J, Ross W (1972) Cytomorphologische und morphometrische Studien der Hepatocarcinogenese. I. Reversible und irreversible Veränderungen am Cytoplasma der Leberparenchymzellen bei Nitrosomorpholin-vergifteten Ratten. Z Krebsforsch 77:108–133

    Article  CAS  Google Scholar 

  • Bannasch P, Benner U, Enzmann H, Hacker HJ (1985) Tigroid cell foci and neoplastic nodules in the liver of rats treated with a single dose of aflatoxin B1. Carcinogenesis 11:1641–1648

    Article  Google Scholar 

  • Bannasch P, Enzmann H, Zerban H (1987) Preneoplastic lesions as indicators of the carcinogenic risk caused by chemicals. In: Bannasch P (ed) Cancer risks. Strategies for elimination. Springer, Berlin Heidelberg New York Tokyo (1987)

    Google Scholar 

  • Betschart JM, Virji MA, Perera MIR, Shinozuka H (1986) Alterations in hepatocyte insulin receptors in rats fed a choline-deficient diet. Cancer Res 46:4425–4430

    PubMed  CAS  Google Scholar 

  • Carlson J, Abraham R (1985) Nuclear ploidy of neonatal rat livers: Effects of two hepatic carcinogens mirex and dimethylnitrosamine. J Toxicol Environ Health 15:551–560

    Article  PubMed  CAS  Google Scholar 

  • Deleener A, Castelain P, Préat V, de Gerlache J, Alexandre H, Kirsch-Volders M (1987) Changes in nucleolar transcriptional activity and nuclear DNA content during the first steps of rat hepatocarcinogenesis. Carcinogenesis 8:195–207

    Article  PubMed  CAS  Google Scholar 

  • Enzmann H, Bannasch P (1986) Sequential phenotypic conversion of hepatocytes during carcinogenesis. Cancer Lett 30:S 67

    Google Scholar 

  • Evarts RP, Marsden ER, Thorgeirsson SS (1985) Modulation of asialoglycoprotein receptor levels in rat liver by phenobarbital treatment. Carcinogenesis 6:1767–1773

    Article  PubMed  CAS  Google Scholar 

  • Grundmann E and Sieburg H (1962) Die Histogenese and Cytogenese des Lebercarcinoms der Ratte durch Diäthylnitrosamin im lichtmikroskopischen Bild. Beitr Pathol Anat 126:57–90

    PubMed  CAS  Google Scholar 

  • Gumucio JJ, Miller DL (1981) Functional implications of liver cell heterogeneity. Gastroenterology 80:393–403

    PubMed  CAS  Google Scholar 

  • Hildebrand R, Karcher B (1984) Karyometry of nuclei in liver cells. Cell Tissue Res 235:669–673

    Article  PubMed  CAS  Google Scholar 

  • James J (1977) The genesis of polyploidy in rat liver parenchymal cells. Eur J Cell Biol 15:410–419

    Google Scholar 

  • James J, Schopman M, Delfgaauw P (1966) The nuclear pattern of the parenchymal cells of the liver after partial hepatectomy. Exp Cell Res 42:375–379

    Article  PubMed  CAS  Google Scholar 

  • James J, Tas J, Bosch KS, de Meere AJP, Schuyt HC (1979) Growth patterns of rat hepatocytes during postnatal development. Eur J Cell Biol 19:222–226

    PubMed  CAS  Google Scholar 

  • Janssen-Timmen U, Traub O, Dermietzel R, Rabes HM, Willecke K (1986) Reduced number of gap junctions in rat hepatocarcinomas detected by monoclonal antibody. Carcinogenesis 7:1475–1482

    Article  PubMed  CAS  Google Scholar 

  • Klinge O (1973a) Kernveränderungen und Kernteilungsstörungen der Altersleber. Gerontologia 19:314–329

    PubMed  CAS  Google Scholar 

  • Klinge O (1973 b) Cytologic and histologic aspects of toxically induced liver reactions. Curr Top Pathol 85:91–116

    Google Scholar 

  • Koike Y, Suzuki Y, Nagata A, Furuta S, Nagata T (1982) Studies of DNA-content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometrie and radioautography. Histochemistry 73:549–562

    Article  PubMed  CAS  Google Scholar 

  • Lev-Ran A, Carr BJ, Hwang DL, Roitman A (1986) Binding of epidermal growth factor and insulin and the autophosphorylation of their receptors in experimental primary hepatocellular carcinomas. Cancer Res 46:4656–4659

    PubMed  CAS  Google Scholar 

  • Miller DL, Harasin JM, Gumucio JJ (1978) Bromobenzeneinduced zonal necrosis in the hepatic acinus. Exp Mol Pathol 29:358–370

    Article  PubMed  CAS  Google Scholar 

  • Moore MA, Kitagawa T (1986) Hepatocarcinogenesis in the rat; the effect of promoters and carcinogens in vivo and in vitro. Int Rev Cytol 101:125–173

    PubMed  CAS  Google Scholar 

  • Mori H, Tanaka T, Sugie S, Takahashi M, Williams GM (1982) DNA content of liver cell nuclei of N-2-fluorenylacetamidinduced altered foci and neoplasms in rats and human hyperplastic foci. J Natl Canc Inst 69:1277–1281

    CAS  Google Scholar 

  • Nostrant TT, Miller DL, Appleman HD, Gumucio JJ (1978) Acinar distribution of liver cell regeneration after selective zonal injury in the rat. Gastroenterology 75:181–186

    PubMed  CAS  Google Scholar 

  • Raymondjean M, Defer N, Tichonicky L, Kruh J, Kneip B, Guguen-Guillonzo C (1985) Changes in poly (A)+ RNA translational pattern during chemically induced hepatocarcinogenesis. Carcinogenesis 6:1797–1803

    Article  PubMed  CAS  Google Scholar 

  • Romen W, Bannasch P, (1972) Karyokinese und Kernstruktur während der Hepatocarcinogenese. Virchows Arch [Cell Pathol] 11:24–33

    CAS  Google Scholar 

  • Romen W, Ross W, Bannasch P (1972) Cytomorphologische und morphometrische Studien der Hepatocarcinogenese II. Die Reversibilität von Kerngrößenveränderungen in der Nitrosomorpholin-vergifteten Rattenleber. Z. Krebsforschung 77:134–140

    Article  CAS  Google Scholar 

  • Scherer E (1984) Neoplastic progression in experimental hepatocarcinogenesis. Biochim Biophys Acta 738:219–236

    PubMed  CAS  Google Scholar 

  • Schwarze PE, Pettersen EO, Shoaib MC, Seglen PO (1984) Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis. Carcinogenesis 5:1267–1275

    Article  PubMed  CAS  Google Scholar 

  • Taper HS, Bannasch P (1979) Histochemical differences between so-called megalocytosis and neoplastic or preneoplastic liver lesions induced by N-nitrosomorpholine. Eur J Cancer 15:189–196

    PubMed  CAS  Google Scholar 

  • Ward JM (1984) Morphology of potential preneoplastic hepatocyte lesions and liver tumours in mice and a comparison with other species. In: Popp JA (ed) Mouse liver neoplasia. Hemisphere, Washington, pp 1–26

  • Watanabe T, Tanaka Y (1982) Age related alterations in the size of human hepatocytes. Virchows Arch [Cell Pathol] 39:9–20

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Enzmann, H., Bannasch, P. Morphometric study of alterations of extrafocal hepatocytes of rat liver treated with N-Nitrosomorpholine. Virchows Archiv B Cell Pathol 53, 218–226 (1987). https://doi.org/10.1007/BF02890246

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02890246

Key words

Navigation