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. 1969 Feb 1;40(2):322–335. doi: 10.1083/jcb.40.2.322

THE FINE STRUCTURE OF PROLIFERATING CELLS IN PRENEOPLASTIC RAT LIVERS DURING AZO-DYE CARCINOGENESIS

Shuichi Karasaki 1
PMCID: PMC2107622  PMID: 4302683

Abstract

The continuous feeding of the carcinogenic aminoazo dye DAB to rats produces hyperbasophilic foci in the preneoplastic livers. After injections of thymidine-3H into the rats, such foci were isolated from the livers and studied by radioautography with the phase-contrast and electron microscopes. In these foci, the only cells found to be proliferating, as determined by the uptake of thymidine-3H into their nuclei, were a poorly differentiated type; well differentiated hepatocytes in the same regions were not labeled with the isotope. The labeled cells had an irregular cell outline and a high nucleocytoplasmic ratio; the cytoplasm had almost completely lost the specialized elements characteristic of hepatocytes; the irregular nuclei with prominent nucleoli, the altered mitochondria, and the increased free ribosomes noted in these cells are features which are characteristic of neoplastic cells induced by DAB. Thus, it seems likely that the hyperbasophilic foci represent the sites of extensive dedifferentiation of hepatocytes followed by rapid cellular proliferation, leading to neoplastic growth.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BRUNI C. Hyaline degeneration of rat liver cells studied with the electron microscope. Lab Invest. 1960 Mar-Apr;9:209–215. [PubMed] [Google Scholar]
  2. Becker F. F., Lane B. P. Regeneration of the mammalian liver. I. Auto-phagocytosis during dedifferentiation of the liver cell in preparation for cell division. Am J Pathol. 1965 Nov;47(5):783–801. [PMC free article] [PubMed] [Google Scholar]
  3. Becker F. F., Lane B. P. Regeneration of the mammalian liver. VI. Retention of phenobarbital-induced cytoplasmic alterations in dividing hepatocytes. Am J Pathol. 1968 Jan;52(1):211–226. [PMC free article] [PubMed] [Google Scholar]
  4. Bruni C., Porter K. R. The Fine Structure of the Parenchymal Cell of the Normal Rat Liver: I. General Observations. Am J Pathol. 1965 May;46(5):691–755. [PMC free article] [PubMed] [Google Scholar]
  5. DAOUST R. CELLULAR POPULATIONS AND NUCLEIC ACID METABOLISM IN RAT LIVER PARENCHYMA DURING AZO DYE CARCINOGENESIS. Proc Can Cancer Conf. 1963;5:225–239. [PubMed] [Google Scholar]
  6. DAOUST R., MOLNAR F. CELLULAR POPULATIONS AND MITOTIC ACTIVITY IN RAT LIVER PARENCHYMA DURING AZO DYE CARCINOGENESIS. Cancer Res. 1964 Dec;24:1898–1909. [PubMed] [Google Scholar]
  7. Essner E. Ultrastructure of spontaneous hyperplastic nodules in mouse liver. Cancer Res. 1967 Nov;27(11):2137–2152. [PubMed] [Google Scholar]
  8. FARBER E. Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylamino-fluorene, and 3'-methyl-4-dimethylaminoazobenzene. Cancer Res. 1956 Feb;16(2):142–148. [PubMed] [Google Scholar]
  9. GRISHAM J. W., PORTA E. A. ORIGIN AND FATE OF PROLIFERATED HEPATIC DUCTAL CELLS IN THE RAT: ELECTRON MICROSCOPIC AND AUTORADIOGRAPHIC STUDIES. Exp Mol Pathol. 1964 Jun;86:242–261. doi: 10.1016/0014-4800(64)90057-7. [DOI] [PubMed] [Google Scholar]
  10. HAY E. D., FISCHMAN D. A. Origin of the blastema in regenerating limbs of the newt Triturus viridescens. An autoradiographic study using tritiated thymidine to follow cell proliferation and migration. Dev Biol. 1961 Feb;3:26–59. doi: 10.1016/0012-1606(61)90009-4. [DOI] [PubMed] [Google Scholar]
  11. HOWATSON A. F., HAM A. W. Electron microscope study of sections of two rat liver tumors. Cancer Res. 1955 Jan;15(1):62–69. [PubMed] [Google Scholar]
  12. Hruban Z., Swift H., Rechcigl M., Jr Fine structure of transplantable hepatomas of the rat. J Natl Cancer Inst. 1965 Sep;35(3):459–495. doi: 10.1093/jnci/35.3.459. [DOI] [PubMed] [Google Scholar]
  13. Inaoka Y. Significance of the so-called oval cell proliferation during azo-dye hepatocarcinogenesis. Gan. 1967 Aug;58(4):355–366. [PubMed] [Google Scholar]
  14. LAFONTAINE J. G., ALLARD C. A LIGHT AND ELECTRON MICROSCOPE STUDY OF THE MORPHOLOGICAL CHANGES INDUCED IN RAT LIVER CELLS BY THE AZO DYE 2-ME-DAB. J Cell Biol. 1964 Jul;22:143–172. doi: 10.1083/jcb.22.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MACDONALD R. A. Experimental carcinoma of the liver. "Regeneration" of liver cells in premalignant stages. Am J Pathol. 1961 Aug;39:209–220. [PMC free article] [PubMed] [Google Scholar]
  16. Ma M. H., Webber A. J. Fine structure of liver tumors induced in the rat by 3'-methyl-4-dimethylaminoazobenzene. Cancer Res. 1966 May;26(5):935–946. [PubMed] [Google Scholar]
  17. Merkow L. P., Epstein S. M., Caito B. J., Bartus B. The cellular analysis of liver carcinogenesis: ultrastructural alterations within hyperplastic liver nodules induced by 2-fluorenylacetamide. Cancer Res. 1967 Sep;27(9):1712–1721. [PubMed] [Google Scholar]
  18. Molnar F., Daoust R. Nucleocytoplasmic ratios in different populations of rat liver parenchymal cells during azo dye carcinogenesis. Cancer Res. 1965 Sep;25(8):1213–1218. [PubMed] [Google Scholar]
  19. NOVIKOFF A. B., ESSNER E. The liver cell. Some new approaches to its study. Am J Med. 1960 Jul;29:102–131. doi: 10.1016/0002-9343(60)90011-5. [DOI] [PubMed] [Google Scholar]
  20. PALADE G. E., SIEKEVITZ P. Liver microsomes; an integrated morphological and biochemical study. J Biophys Biochem Cytol. 1956 Mar 25;2(2):171–200. doi: 10.1083/jcb.2.2.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. SVOBODA D. J. FINE STRUCTURE OF HEPATOMAS INDUCED IN RATS WITH P-DIMETHYLAMINOAZOBENZENE. J Natl Cancer Inst. 1964 Aug;33:315–338. [PubMed] [Google Scholar]
  22. Simard A., Daoust R. DNA synthesis and neoplastic transformation in rat liver parenchyma. Cancer Res. 1966 Aug;26(8):1665–1672. [PubMed] [Google Scholar]
  23. Steiner J. W., Perz Z. M., Taichman L. B. Cell population dynamics in the liver. A review of quantitative morphological techniques applied to the study of physiological and pathological growth. Exp Mol Pathol. 1966 Apr;5(2):146–181. doi: 10.1016/0014-4800(66)90012-8. [DOI] [PubMed] [Google Scholar]
  24. Stenger R. J., Confer D. B. Hepatocellular ultrastructure during liver regeneration after subtotal hepatectomy. Exp Mol Pathol. 1966 Oct;5(5):455–474. doi: 10.1016/0014-4800(66)90026-8. [DOI] [PubMed] [Google Scholar]

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