Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1985 Feb;118(2):218–224.

Connection of ductlike structures induced by a chemical hepatocarcinogen to portal bile ducts in the rat liver detected by injection of bile ducts with a pigmented barium gelatin medium.

H A Dunsford, R Maset, J Salman, S Sell
PMCID: PMC1887865  PMID: 2578739

Abstract

Newly found metaplastic ductlike structures that form in the liver of rats exposed to carcinogens are connected to preexisting bile ducts. Male Fischer rats fed a diet of N-2-acetylaminofluorene in a choline-deficient diet (CDAAF) develop a massive proliferation of oval cells which appear to differentiate into bile-ductlike structures. However, unlike normal or proliferating bile ducts, these ductlike structures contain alpha-fetoprotein (AFP) and albumin, which are markers for proliferating hepatocytes and some hepatocellular carcinomas. Bile duct injections with a green pigmented barium gelatin medium filled the lumens of the ductlike structures and typical ductlike structures induced by the CDAAF diet, as well as the proliferating bile ducts induced by the noncarcinogenic alpha-naphthylisothiocyanate (ANIT), and the ducts in the normal controls. AFP was present in the ductlike structures in the rats fed AAF, but not in the bile ducts of animals fed ANIT. These studies suggest that most, if not all, of the ductlike structures produced during chemical hepatocarcinogenesis are derived from bile ducts, yet have the capacity to produce AFP and albumin.

Full text

PDF
218

Images in this article

220Figure 1
on p.220
220Figure 2
on p.220
220Figure 3
on p.220
220Figure 4
on p.220
222Figure 6
on p.222
222Figure 7
on p.222

Selected References

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

  1. Campbell H. A., Pitot H. C., Potter V. R., Laishes B. A. Application of quantitative stereology to the evaluation of enzyme-altered foci in rat liver. Cancer Res. 1982 Feb;42(2):465–472. [PubMed] [Google Scholar]
  2. Dempo K., Chisaka N., Yoshida Y., Kaneko A., Onoé T. Immunofluorescent study on alpha-fetoprotein-producing cells in the early stage of 3'-methyl-4-dimethylaminoazobenzene carcinogenesis. Cancer Res. 1975 May;35(5):1282–1287. [PubMed] [Google Scholar]
  3. 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]
  4. FIRMINGER H. I. Histopathology of carcinogenesis and tumors of the liver in rats. J Natl Cancer Inst. 1955 Apr;15(5 Suppl):1427–1442. [PubMed] [Google Scholar]
  5. Farber E. The sequential analysis of liver cancer induction. Biochim Biophys Acta. 1980 May 6;605(2):149–166. doi: 10.1016/0304-419x(80)90002-5. [DOI] [PubMed] [Google Scholar]
  6. GRISHAM J. W., HARTROFT W. S. Morphologic identification by electron microscopy of "oval" cells in experimental hepatic degeneration. Lab Invest. 1961 Mar-Apr;10:317–332. [PubMed] [Google Scholar]
  7. 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]
  8. Hales M. R., Carrington C. B. A pigmented gelatin mass for vascular injection. Yale J Biol Med. 1971 Feb-Apr;43(4-5):257–270. [PMC free article] [PubMed] [Google Scholar]
  9. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  10. Lombardi B., Shinozuka H. Enhancement of 2-acetylaminofluorene liver carcinogenesis in rats fed a choline-devoid diet. Int J Cancer. 1979 Apr 15;23(4):565–570. doi: 10.1002/ijc.2910230419. [DOI] [PubMed] [Google Scholar]
  11. McLEAN M. R., REES K. R. Hyperplasia of bile-ducts induced by alpha-naphthyl-iso-thiocyanate: experimental biliary cirrhosis free from biliary obstruction. J Pathol Bacteriol. 1958 Jul;76(1):175–188. doi: 10.1002/path.1700760120. [DOI] [PubMed] [Google Scholar]
  12. Ogawa K., Solt D. B., Farber E. Phenotypic diversity as an early property of putative preneoplastic hepatocyte populations in liver carcinogenesis. Cancer Res. 1980 Mar;40(3):725–733. [PubMed] [Google Scholar]
  13. POPPER H., KENT G., STEIN R. Ductular cell reaction in the liver in hepatic injury. J Mt Sinai Hosp N Y. 1957 Sep-Oct;24(5):551–556. [PubMed] [Google Scholar]
  14. REUBER M. D., FIRMINGER H. I. MORPHOLOGIC AND BIOLOGIC CORRELATION OF LESIONS OBTAINED IN HEPATIC CARCINOGENESIS IN A X C RATS GIVEN 0.025 PERCENT N-2-FLUORENYLDIACETAMIDE. J Natl Cancer Inst. 1963 Dec;31:1407–1429. [PubMed] [Google Scholar]
  15. Richards W. L., Tsukada Y., Potter V. R. gamma-Glutamyl transpeptidase and alpha-fetoprotein expression during alpha-naphthylisothiocyanate-induced hepatotoxicity in rats. Cancer Res. 1982 Dec;42(12):5133–5138. [PubMed] [Google Scholar]
  16. STEIN R. J., KENT G., POPPER H. Effect of cortisone and growth hormone upon ductular cell proliferation in liver ethionine intoxication. Proc Soc Exp Biol Med. 1958 Oct;99(1):24–28. doi: 10.3181/00379727-99-24233. [DOI] [PubMed] [Google Scholar]
  17. Sell S. Comparison of oval cells induced in rat liver by feeding N-2-fluorenylacetamide in a choline-devoid diet and bile duct cells induced by feeding 4,4'-diaminodiphenylmethane. Cancer Res. 1983 Apr;43(4):1761–1767. [PubMed] [Google Scholar]
  18. Sell S. Distribution of alpha-fetoprotein- and albumin-containing cells in the livers of Fischer rats fed four cycles of N-2-fluorenylacetamide. Cancer Res. 1978 Sep;38(9):3107–3113. [PubMed] [Google Scholar]
  19. Sell S. Heterogeneity of alpha-fetoprotein(AFP) and albumin containing cells in normal and pathological permissive states for AFP production: AFP containing cells induced in adult rats recapitulate the appearance of AFP containing hepatocytes in fetal rats. Oncodev Biol Med. 1980;1(2):93–105. [PubMed] [Google Scholar]
  20. Sell S., Leffert H. L. An evaluation of cellular lineages in the pathogenesis of experimental hepatocellular carcinoma. Hepatology. 1982 Jan-Feb;2(1):77–86. doi: 10.1002/hep.1840020113. [DOI] [PubMed] [Google Scholar]
  21. Sell S., Leffert H. L., Shinozuka H., Lombardi B., Gochman N. Rapid development of large numbers of alpha-fetoprotein-containing "oval" cells in the liver of rats fed N-2-fluorenylacetamide in a choline-devoid diet. Gan. 1981 Aug;72(4):479–487. [PubMed] [Google Scholar]
  22. Sell S., Nichols M., Becker F. F., Leffert H. L. Hepatocyte proliferation and alpha 1-fetoprotein in pregnant, neonatal, and partially hepatectomized rats. Cancer Res. 1974 Apr;34(4):865–871. [PubMed] [Google Scholar]
  23. Sell S., Osborn K., Leffert H. L. Autoradiography of "oval cells" appearing rapidly in the livers of rats fed N-2-fluorenylacetamide in a choline devoid diet. Carcinogenesis. 1981;2(1):7–14. doi: 10.1093/carcin/2.1.7. [DOI] [PubMed] [Google Scholar]
  24. Sell S., Salman J. Light- and electron-microscopic autoradiographic analysis of proliferating cells during the early stages of chemical hepatocarcinogenesis in the rat induced by feeding N-2-fluorenylacetamide in a choline-deficient diet. Am J Pathol. 1984 Feb;114(2):287–300. [PMC free article] [PubMed] [Google Scholar]
  25. Shinozuka H., Lombardi B., Sell S., Iammarino R. M. Early histological and functional alterations of ethionine liver carcinogenesis in rats fed a choline-deficient diet. Cancer Res. 1978 Apr;38(4):1092–1098. [PubMed] [Google Scholar]
  26. Shinozuka H., Sells M. A., Katyal S. L., Sell S., Lombardi B. Effects of a choline-devoid diet on the emergence of gamma-glutamyltranspeptidase-positive foci in the liver of carcinogen-treated rats. Cancer Res. 1979 Jul;39(7 Pt 1):2515–2521. [PubMed] [Google Scholar]
  27. Tchipysheva T. A., Guelstein V. I., Bannikov G. A. alpha-fetoprotein-containing cells in the early stages of liver carcinogenesis induced by 3'-methyl-4-dimethyl-aminoazobenzene and 2-acetylaminofluorene. Int J Cancer. 1977 Sep 15;20(3):388–393. doi: 10.1002/ijc.2910200310. [DOI] [PubMed] [Google Scholar]
  28. Williams G. M., Watanabe K. Quantitative kinetics of development of N-2-fluorenylacetamide-induced, altered (hyperplastic) hepatocellular foci resistant to iron accumulation and of their reversion or persistence following removal of carcinogen. J Natl Cancer Inst. 1978 Jul;61(1):113–121. doi: 10.1093/jnci/61.1.113. [DOI] [PubMed] [Google Scholar]
  29. Williams G. M., Yamamoto R. S. Absence of stainable iron from preneoplastic and neoplastic lesions in rat liver with 8-hydroxyquinoline-induced siderosis. J Natl Cancer Inst. 1972 Sep;49(3):685–692. [PubMed] [Google Scholar]
  30. Wu P. C., Ma L., Gibson J. B., Hirai H., Tsukada Y. Serum alpha-fetoprotein in rats after ligation of the common bile duct: relation to ductular cell (oval cell) proliferation. J Pathol. 1981 Jan;133(1):61–74. doi: 10.1002/path.1711330107. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES