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Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus

  • Original Papers
  • Experimental Oncology
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Summary

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) was associated with the development of hepatitis, foci of altered hepatocytes and hepatocellular adenomas and carcinomas. The cytomorphological and cytochemical analysis permitted the identification of three different types of focal lesions; namely, glycogen-storage foci, mixed-cell foci and intermediatecell foci, each showing a characteristic pattern. The cells of the glycogen-storage foci had clear to acidophilic cytoplasm, and were overloaded with glycogen. They showed a marked elevation in the activity of glucose-6-phosphate dehydrogenase (G6PDH) and malate dehydrogenase (MDH), increased activity of succinate dehydrogenase (SDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycerol-3-phosphate dehydrogenase (G3PDH), reduction in the activity of glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and adenyl cyclase (ADC), and unchanged activity of glycogen synthase (SYN) andγ-glutamyl transferase (GGT). The mixed-cell foci mainly consisted of basophilic cells poor in glycogen, but were intermingled with cells containing glycogen. These foci were characterized by a marked decrease in activity of PHO, SYN, G6Pase, G6PDH, ATPase and ADC, and increased activity of GGT, SDH, MDH and GAPDH. The intermediate-cell foci consisted of cells with both basophilic and glycogenotic cytoplasmic compartments, and showed a similar enzyme histochemical profile to the mixed-cell foci, with slight differences in the degree of elevation or reduction of some enzymes. The phenotypic similarities and the close spatial relationship between the foci of altered hepatocytes, and the hepatocellular adenomas and carcinomas in WHV-infected woodchucks, suggest that these lesions are preneoplastic. The focal morphological and metabolic aberrations emerging during hepatocarcinogenesis in WHV-infected woodchuck, are in principle similar to those identified in the course of chemical hepatocarcinogenesis in various species. The focal metabolic aberrations apparently represent a general biological response of the liver parenchyma to oncogenic agents and are closely linked to neoplasic transformation of the hepatocytes.

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Abbreviations

WHV:

woodchuck hepatitis virus

GSF:

glycogen-storage foci

MCF:

mixed-cell foci

ICF:

intermediate-cell foci

PAS:

periodic acid Schiffs reaction

PHO:

glycogen phosphorylase

SYN:

glycogen synthase

G6Pase:

glucose-6-phosphatase

G6PDH:

glucose-6-phosphate dehydrogenase

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

MDH:

malate dehydrogenase

SDH:

succinate dehydrogenase

G3PDH:

glycerol-3-phosphate dehydrogenase

ADC:

adenyl cyclase

GGT:

γ-glutamyl transferase

ALP:

alkaline phosphatase

ACP:

acid phosphatase

ATPase:

adenosine triphosphatase

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Authors and Affiliations

  1. Abteilung für Cytopathologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-6900, Heidelberg 1, Federal Republic of Germany

    I. Toshkov (Fellow of the Alexander von Humboldt-Stiftung and guest research scientist of Deutsches Krebsforschungszentrum), H. J. Hacker & P. Bannasch

  2. Max-von-Pettenkofer-Institut, Universität München, Pettenkoferstraße 9a, D-8000, München 2, Federal Republic of Germany

    M. Roggendorf

Authors
  1. I. Toshkov
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  2. H. J. Hacker
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  3. M. Roggendorf
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  4. P. Bannasch
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Dedicated to Professor Dietrich Schmähl on the occasion of his 65th birthday

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Toshkov, I., Hacker, H.J., Roggendorf, M. et al. Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus. J Cancer Res Clin Oncol 116, 581–590 (1990). https://doi.org/10.1007/BF01637078

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  • DOI: https://doi.org/10.1007/BF01637078

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