Skip to main content

Advertisement

Log in

Immunocytochemical investigation ofα-fetoprotein-positive cells in hepatocarcinogenesis and hepatomas induced by 3′-Me-DAB

  • Original Article
  • Published:
Gastroenterologia Japonica Aims and scope Submit manuscript

Summary

AFP-positive cells during 3′-Me-DAB hepatocarcinogenesis and in hepatomas induced by 3′ -Me-DAB were observed by the light microscope immunoperoxidase method, and the location of AFP-immunoreaction products in hepatocytes was determined by the electron microscope immunoperoxidase method. Simultaneously serum concentrations of AFP were measured by radioimmunoassay.

Serum concentrations of AFP during hepatocarcinogenesis showed a biphasic pattern, and proliferation of cholangiolar cells in the periportal areas was associated with the first peak of serum AFP in the early stage of hepatocarcinogenesis. AFP-containing cells in the late stage were distributed in clusters in the peripheral areas of hyperplastic nodules. The clusters were composed of two different types of AFP-positive cells, one atypical in shape and structure and the other preserving the structure of hepatic cords. In neoplasms, a heterogeneous AFP immunoreaction was recognized in hepatoma cells. In non-neoplastic nodules, cholangiofibrosis surrounded by AFP-positive cholangiolar cells developed.

Ultrastructural immunoperoxidase studies revealed immunoreaction products of AFP on the membrane of r-ER, outer nuclear membrane, s-ER and Golgi complex in hepatocytes of hyperplastic nodules as well as of hepatocellular carcinoma cells.

It is suggested that cholangiolar cells detected in hepatocarcinogenesis may form proliferating bile ductules, and the appearance of a cluster in association with AFP in hyperplastic nodules supports the hypothesis that some hyperplastic nodules with clusters of AFP-positive cells are important cell populations which may develop into hepatocellular carcinoma.

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

  1. Farber E: Hyperplastic liver nodules. Methods in Cancer Res 7: 345, 1973

    CAS  Google Scholar 

  2. Farber E: Similarities in the sequence of early histological changes in the liver of the rat by ethionine, 2-acetylaminofluorene and 3-methyl-4-dimethylaminoazobenzene. Cancer Res 16: 142, 1956

    PubMed  CAS  Google Scholar 

  3. Farber E: The sequential analysis of liver cancer induction. Biochemica et Biophysica Acta 605: 149, 1980

    CAS  Google Scholar 

  4. Okita K, et al: An antigen common to preneoplastic hepatocyte population and to liver cancer induced by N-2-fluorenylacetamide, ethionine, or other hepatocarcinogenesis. Gann Monograph on Cancer Res 17: 283, 1975

    CAS  Google Scholar 

  5. Enomoto K, et al: et al: Immunohistochemical study of epoxide hydrolase during experimental liver carcinogenesis. Cancer Res 41: 3281, 1981

    PubMed  CAS  Google Scholar 

  6. Abelev GI, et al: Production of embryonal α-globulin by transplantable mouse hepatomas. Transplantation 1: 174, 1963

    Article  PubMed  CAS  Google Scholar 

  7. Abelev GI: AFP in ontogenesis and its association with malaignant tumors. Adv Cancer Res 14: 295, 1971

    PubMed  CAS  Google Scholar 

  8. Ruoslahti E, et al: α-fetoprotein in cancer and fetal development. Adv Cancer Res 29: 275, 1979

    PubMed  CAS  Google Scholar 

  9. Elliot A: Human alpha-fetoprotein (AFP): Development biology and clinical significance. Progress in liver diseases Vol 5: 337, 1976

    Google Scholar 

  10. Kuhlman WD: α-fetoprotein: Cellular origin of a biological marker in rat liver under various experimental conditions. Virchows Arch A 393: 9, 1981

    Google Scholar 

  11. Hirai H, et al: Some chemical, experimental, and clinical investigation of α-fetoprotein. Gann Monograph on Cancer Res 14: 19, 1973

    Google Scholar 

  12. Sell S: Distribution of α-fetoprotein and albumin-containing cells in the livers of Fisher rats fed four cycles of N-2-fluorenylacetamide. Cancer Res 38: 3107, 1973

    Google Scholar 

  13. Onda H: Immunohistological studies of α-fetoprotein and α-acid glycoprotein during azo dye hepatocarcinogenesis in rats. Gann 67: 253, 1976

    PubMed  CAS  Google Scholar 

  14. Sell S, et al: Rapid development of large number of α-fetoprotein-containing “oval” cells in the liver of rats fed N-2-fluorenylacetamide in a choline-devoid diet. Gann 72: 479, 1981

    PubMed  CAS  Google Scholar 

  15. Dempo K, et al: Immunofluorescent study of α-fetoprotein-producing cells in the early stage of 3′-methyl-4-dimethyl-aminoazobenzene carcinogenesis. Cancer Res 35: 1282, 1975

    PubMed  CAS  Google Scholar 

  16. Ishii M, et al: Isolation and microheterogeneity of rat α-fetoprotein. Tumor Res 8: 68, 1973

    CAS  Google Scholar 

  17. Ishii M, et al: Change of serum AFP levels in carbon tetrachloride induced hepatitis. Tumor Res 8: 114, 1973

    CAS  Google Scholar 

  18. Stewert H, et al: Histologic typing of liver tumors of the rat. J Natl Cancer Inst 64a: 177, 1980

    Google Scholar 

  19. Price JM, et al: Progressive microscopic alterations in the livers of rats fed the hepatic carcinogenes, 3′-methyl-4-dimethylaminoazobenzene and 4′-fluore-4-dimethyl-aminoazobenzene. Cancer Res 12: 92, 1952

    Google Scholar 

  20. Onoe T, et al: α-fetoprotein and early histological changes of hepatic tissue in DAB-hepatocarcinogenesis. Ann NY Acad Sci 259: 168, 1973

    Article  Google Scholar 

  21. Inaoka Y: Significance of the so-called oval cell proliferation during azo dye hepatocarcinogenesis. Gann 58: 355, 1976

    Google Scholar 

  22. Hadjiolov DC: Histochemical studies of some oxidative enzymes in the early proliferative stage of liver carcinogenesis. Z Krebsforsh 66: 473, 1965

    Article  CAS  Google Scholar 

  23. Takahashi S, et al: Growth of DL-ethionine induced oval cells transplanted heterotopically in syngeneic rats. Acta Hepatologica Jpn 6: 242, 1982

    Google Scholar 

  24. Terao K, et al: Cholangiofibrosis induced by shortterm feeding of 3′-methyl-4-dimethylaminoazobenzene: an electron microscopic observation. Gann 65: 249, 1974

    PubMed  CAS  Google Scholar 

  25. Kitagawa T: Sequential phenotypic changes in hyperplastic areas during hepatocarcinogenesis. Cancer Res 36: 2534, 1976

    PubMed  CAS  Google Scholar 

  26. Søguard PE: Nodular transformation of the liver, α-fetoprotein, and hepatocellular carcinoma. Human Pathol 12: 1052, 1981

    Article  Google Scholar 

  27. Ying TS, et al: Effects of changes in the cell cycle on the induction of preneoplastic and neoplastic lesions in rat liver by 1, 2-dimethylhydrazine. Cancer Res 42: 876, 1982

    PubMed  CAS  Google Scholar 

  28. Scherer E: Kinetics of induction and growth of enzyme deficient islands involved in hepatocarcinogenesis. Cancer Res 36: 2544, 1976

    PubMed  CAS  Google Scholar 

  29. Pitot HC, et al: Biochemical characterization of stage of hepatocarcinogenesis after a single dose of diethylnitrosamine. Nature 271: 450, 1978

    Article  Google Scholar 

  30. Harada M, et al: Histochemical demonstration of γ-glutamyl transpeptidase in rat liver during hepatocarcinogenesis. Acta Histochem Cytochem 9: 168, 1976

    CAS  Google Scholar 

  31. Levin W, et al: Identification of epoxide hydrolase as the preneoplastic antigen in rat liver hyperplastic nodules. Proc Natl Sci 75: 3240, 1973

    Article  Google Scholar 

  32. Okita K, et al: A new common marker for premalignant and malignant hepatocytes induced in the rat by chemical carcinogen. J Nat Cancer Inst 54: 199, 1979

    Google Scholar 

  33. Okita K, et al: Localization of α-fetoprotein by immunofluorescence in hyperplastic nodules during hepatocarcinogenesis induced by 2-acetylaminofluorence. Cancer Res 34: 2758, 1974

    PubMed  CAS  Google Scholar 

  34. Teebor GW, et al: Regression and persistence of hyperlastic nodules induced by N-2-fluorenylacetamide and their relationship to hepatocarcinogenesis. Cancer Res 31: 1, 1971

    PubMed  CAS  Google Scholar 

  35. Tuczek HV, et al: Synthesis of α-fetoprotein (AFP) and cell proliferation in regenerating livers of NMRI mice after partial hepatectomy. Virchows Arch (Cell Pathol) 38: 229, 1981

    Article  CAS  Google Scholar 

  36. Kuhlmann WD: Immunoperoxidase labelling of α-fetoprotein (AFP) in normal and regenerating livers of a low and a high AFP producing mouse strain. Histochemistry 64: 67, 1979

    Article  PubMed  CAS  Google Scholar 

  37. Edward A, et al: α-fetoprotein in toxic liver injury. Cancer Res 36: 4558, 1976

    Google Scholar 

  38. Sell S, et al: Relationship of rat α-fetoprotein to growth rate and chromosome composition of morris hepatomas. Cancer Res 34: 1413, 1974

    PubMed  CAS  Google Scholar 

  39. Becker FF, et al: Characterization of primary hepatocellular carcinoma and initial plant generations. Cancer Res 33: 3330, 1973

    PubMed  CAS  Google Scholar 

  40. Tsukada Y, et al: α-fetoprotein and albumin synthesis during the cell cycle. Ann NY Acad Sci 259: 37, 1975

    Article  PubMed  CAS  Google Scholar 

  41. Ogawa K, et al: Soquential analysis of hepatic carcinogenesis. —A comparative study of the ultrastructure of preneoplastic, malignant, prenatal, postnatal, and regenerating liver—. Lab Invest 41: 22, 1979

    PubMed  CAS  Google Scholar 

  42. Fuse Y, et al: Liver tumors in rats by 3′-methylaminoazobenzene. II. Electron microscopic investigation Differentiation of cancer cells - Tumor Res 3: 145 1968

    Google Scholar 

  43. Farber E, et al: Cellular analysis of liver carcinogenesis. III. Comparison of the ultrastructure of hyperplastic liver nodules and hepatocellular carcinomas induced in rat liver by 2-fluorenylacetamide. J Nat Cancer Inst 43: 33, 1969

    PubMed  Google Scholar 

  44. Shikata T: Immunoelectronmicroscopic study of afetoprotein synthesis in hepatoma cells. Ann NY Acad Sci 259: 211, 1975

    Article  PubMed  CAS  Google Scholar 

  45. Kuhlmann WD: Ultrastructural detections of α1-fetoprotein in hepatomas by use of peroxidase-labelled antibodies. Int J Cancer 22: 335, 1978

    Article  PubMed  CAS  Google Scholar 

  46. Peyrol JA, et al: Tissular immunoenzymatic detection of hepatic alpha-fetoprotein in human hepatomas. Digestion 18: 351, 1978

    PubMed  CAS  Google Scholar 

  47. Nemoto N, et al: Occurrence of alpha-fetoproteincontaining hepatocytes in human embryos and fetuses. An immunohistochemical study using the light and ultrastructural immunoperoxidase methods. J Histochem Cytochem 30: 1022, 1982

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iwai, M. Immunocytochemical investigation ofα-fetoprotein-positive cells in hepatocarcinogenesis and hepatomas induced by 3′-Me-DAB. Gastroenterol Jpn 18, 346–358 (1983). https://doi.org/10.1007/BF02774952

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02774952

Key Words

Navigation