Cellular origin of cancer: dedifferentiation or stem cell maturation arrest? (original) (raw)

Abstract

Given the fundamental principle that cancer must arise from a cell that has the potential to divide, two major nonexclusive hypotheses of the cellular origin of cancer are that malignancy arises a) from stem cells due to maturation arrest or b) from dedifferentiation of mature cells that retain the ability to proliferate. The role of stem cells in carcinogenesis is clearly demonstrated in teratocarcinomas. The malignant stem cells of teratocarcinomas are derived from normal multipotent stem cells and have the potential to differentiate into normal benign mature tissue. A widely studied model supporting dedifferentiation has been the putative origin of hepatocarcinomas from "premalignant" foci and nodules induced in the rat liver by chemicals. However, the dedifferentiation concept for hepatocarcinogenesis is challenged by more recent interpretations indicating that hepatocellular carcinoma arises from maturation arrest caused by aberrant differentiation of determined stem cells. Either hypothesis is supported by the cellular changes that occur in the rodent liver after different hepatocarcinogenic regimens. The formation of foci and nodules from altered hepatocytes supports dedifferentiation; the proliferation of small oval cells with the potential to differentiate into either biliary ducts or hepatocytes supports arrested maturation of determined stem cells. It is now postulated that foci and nodular change reflect adaptive changes to the toxic effects of carcinogens and not "preneoplastic" stages to cancer. The stem cell model predicts that genotoxic chemicals induce mutations in the determined stem cell which may be expressed in its progeny. Proliferation of initiated cells is induced by promoting events which also allow additional mutations to occur.

15

Selected References

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

  1. Arber N., Zajicek G., Nordenberg J., Sidi Y. Azathioprine treatment increases hepatocyte turnover. Gastroenterology. 1991 Oct;101(4):1083–1086. doi: 10.1016/0016-5085(91)90737-6. [DOI] [PubMed] [Google Scholar]
  2. Bannasch P. Sequential cellular changes during chemical carcinogenesis. J Cancer Res Clin Oncol. 1984;108(1):11–22. doi: 10.1007/BF00390968. [DOI] [PubMed] [Google Scholar]
  3. Bishop J. M. Viral oncogenes. Cell. 1985 Aug;42(1):23–38. doi: 10.1016/s0092-8674(85)80098-2. [DOI] [PubMed] [Google Scholar]
  4. Brinster R. L. The effect of cells transferred into the mouse blastocyst on subsequent development. J Exp Med. 1974 Oct 1;140(4):1049–1056. doi: 10.1084/jem.140.4.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bréchot C., Hadchouel M., Scotto J., Fonck M., Potet F., Vyas G. N., Tiollais P. State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3906–3910. doi: 10.1073/pnas.78.6.3906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bréchot C. Hepatitis B virus (HBV) and hepatocellular carcinoma. HBV DNA status and its implications. J Hepatol. 1987 Apr;4(2):269–279. doi: 10.1016/s0168-8278(87)80090-9. [DOI] [PubMed] [Google Scholar]
  7. Callea F., Brisigotti M., Fabbretti G., Sciot R., Van Eyken P., Favret M. Cirrhosis of the liver. A regenerative process. Dig Dis Sci. 1991 Sep;36(9):1287–1293. doi: 10.1007/BF01307524. [DOI] [PubMed] [Google Scholar]
  8. Cattley R. C., Smith-Oliver T., Butterworth B. E., Popp J. A. Failure of the peroxisome proliferator WY-14,643 to induce unscheduled DNA synthesis in rat hepatocytes following in vivo treatment. Carcinogenesis. 1988 Jul;9(7):1179–1183. doi: 10.1093/carcin/9.7.1179. [DOI] [PubMed] [Google Scholar]
  9. Chisari F. V., Filippi P., Buras J., McLachlan A., Popper H., Pinkert C. A., Palmiter R. D., Brinster R. L. Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6909–6913. doi: 10.1073/pnas.84.19.6909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chisari F. V., Klopchin K., Moriyama T., Pasquinelli C., Dunsford H. A., Sell S., Pinkert C. A., Brinster R. L., Palmiter R. D. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell. 1989 Dec 22;59(6):1145–1156. doi: 10.1016/0092-8674(89)90770-8. [DOI] [PubMed] [Google Scholar]
  11. Chisari F. V., Pinkert C. A., Milich D. R., Filippi P., McLachlan A., Palmiter R. D., Brinster R. L. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science. 1985 Dec 6;230(4730):1157–1160. doi: 10.1126/science.3865369. [DOI] [PubMed] [Google Scholar]
  12. Cohen S. M., Ellwein L. B. Genetic errors, cell proliferation, and carcinogenesis. Cancer Res. 1991 Dec 15;51(24):6493–6505. [PubMed] [Google Scholar]
  13. 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]
  14. Dragani T. A., Manenti G., Farza H., Della Porta G., Tiollais P., Pourcel C. Transgenic mice containing hepatitis B virus sequences are more susceptible to carcinogen-induced hepatocarcinogenesis. Carcinogenesis. 1990 Jun;11(6):953–956. doi: 10.1093/carcin/11.6.953. [DOI] [PubMed] [Google Scholar]
  15. Dunsford H. A., Karnasuta C., Hunt J. M., Sell S. Different lineages of chemically induced hepatocellular carcinoma in rats defined by monoclonal antibodies. Cancer Res. 1989 Sep 1;49(17):4894–4900. [PubMed] [Google Scholar]
  16. Dunsford H. A., Maset R., Salman J., Sell S. 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. Am J Pathol. 1985 Feb;118(2):218–224. [PMC free article] [PubMed] [Google Scholar]
  17. Dunsford H. A., Sell S., Chisari F. V. Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice. Cancer Res. 1990 Jun 1;50(11):3400–3407. [PubMed] [Google Scholar]
  18. Dunsford H. A., Sell S. Production of monoclonal antibodies to preneoplastic liver cell populations induced by chemical carcinogens in rats and to transplantable Morris hepatomas. Cancer Res. 1989 Sep 1;49(17):4887–4893. [PubMed] [Google Scholar]
  19. Elmore L. W., Sirica A. E. Phenotypic characterization of metaplastic intestinal glands and ductular hepatocytes in cholangiofibrotic lesions rapidly induced in the caudate liver lobe of rats treated with furan. Cancer Res. 1991 Oct 15;51(20):5752–5759. [PubMed] [Google Scholar]
  20. Engelhardt N. V., Baranov V. N., Lazareva M. N., Goussev A. I. Ultrastructural localisation of alpha-fetoprotin (AFP) in regenerating mouse liver poisoned with CCL4. 1. Reexpression of AFP in differentiated hepatocytes. Histochemistry. 1984;80(4):401–407. doi: 10.1007/BF00495425. [DOI] [PubMed] [Google Scholar]
  21. Esumi M., Aritaka T., Arii M., Suzuki K., Tanikawa K., Mizuo H., Mima T., Shikata T. Clonal origin of human hepatoma determined by integration of hepatitis B virus DNA. Cancer Res. 1986 Nov;46(11):5767–5771. [PubMed] [Google Scholar]
  22. Evarts R. P., Nagy P., Marsden E., Thorgeirsson S. S. A precursor-product relationship exists between oval cells and hepatocytes in rat liver. Carcinogenesis. 1987 Nov;8(11):1737–1740. doi: 10.1093/carcin/8.11.1737. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Fabrikant J. I. The kinetics of cellular proliferation in regenerating liver. J Cell Biol. 1968 Mar;36(3):551–565. doi: 10.1083/jcb.36.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Farber E. Pathogenesis of liver cancer. Arch Pathol. 1974 Sep;98(3):145–148. [PubMed] [Google Scholar]
  26. Farber E. Pre-cancerous steps in carcinogenesis. Their physiological adaptive nature. Biochim Biophys Acta. 1984;738(4):171–180. doi: 10.1016/0304-419x(83)90002-1. [DOI] [PubMed] [Google Scholar]
  27. Fausto N. Hepatocyte differentiation and liver progenitor cells. Curr Opin Cell Biol. 1990 Dec;2(6):1036–1042. doi: 10.1016/0955-0674(90)90153-6. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Germain L., Blouin M. J., Marceau N. Biliary epithelial and hepatocytic cell lineage relationships in embryonic rat liver as determined by the differential expression of cytokeratins, alpha-fetoprotein, albumin, and cell surface-exposed components. Cancer Res. 1988 Sep 1;48(17):4909–4918. [PubMed] [Google Scholar]
  30. Hixson D. C., Allison J. P. Monoclonal antibodies recognizing oval cells induced in the liver of rats by N-2-fluorenylacetamide or ethionine in a choline-deficient diet. Cancer Res. 1985 Aug;45(8):3750–3760. [PubMed] [Google Scholar]
  31. Jalanko H., Ruoslahti E. Differential expression of alpha-fetoprotein and gamma-glutamyltranspeptidase in chemical and spontaneous hepatocarcinogenesis. Cancer Res. 1979 Sep;39(9):3495–3501. [PubMed] [Google Scholar]
  32. Kew M. C., Popper H. Relationship between hepatocellular carcinoma and cirrhosis. Semin Liver Dis. 1984 May;4(2):136–146. doi: 10.1055/s-2008-1040653. [DOI] [PubMed] [Google Scholar]
  33. Kim C. M., Koike K., Saito I., Miyamura T., Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature. 1991 May 23;351(6324):317–320. doi: 10.1038/351317a0. [DOI] [PubMed] [Google Scholar]
  34. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kuhlmann W. D. Localization of alpha1-fetoprotein and DNA-synthesis in liver cell populations during experimental hepatocarcinogenesis in rats. Int J Cancer. 1978 Mar 15;21(3):368–380. doi: 10.1002/ijc.2910210319. [DOI] [PubMed] [Google Scholar]
  36. Lee T. H., Finegold M. J., Shen R. F., DeMayo J. L., Woo S. L., Butel J. S. Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. J Virol. 1990 Dec;64(12):5939–5947. doi: 10.1128/jvi.64.12.5939-5947.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lemire J. M., Shiojiri N., Fausto N. Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine. Am J Pathol. 1991 Sep;139(3):535–552. [PMC free article] [PubMed] [Google Scholar]
  38. Marceau N. Cell lineages and differentiation programs in epidermal, urothelial and hepatic tissues and their neoplasms. Lab Invest. 1990 Jul;63(1):4–20. [PubMed] [Google Scholar]
  39. 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]
  40. Mintz B., Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3585–3589. doi: 10.1073/pnas.72.9.3585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Novikoff P. M., Ikeda T., Hixson D. C., Yam A. Characterizations of and interactions between bile ductule cells and hepatocytes in early stages of rat hepatocarcinogenesis induced by ethionine. Am J Pathol. 1991 Dec;139(6):1351–1368. [PMC free article] [PubMed] [Google Scholar]
  42. O'Hare M. J. Teratomas, neoplasia and differentiation: a biological overview. I. The natural history of teratomas. Invest Cell Pathol. 1978 Jan-Mar;1(1):39–63. [PubMed] [Google Scholar]
  43. PIERCE G. B., DIXON F. J., Jr Testicular teratomas. I. Demonstration of teratogenesis by metamorphosis of multipotential cells. Cancer. 1959 May-Jun;12(3):573–583. doi: 10.1002/1097-0142(195905/06)12:3<573::aid-cncr2820120316>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  44. PIERCE G. B., Jr, DIXON F. J., Jr, VERNEY E. L. Teratocarcinogenic and tissue-forming potentials of the cell types comprising neoplastic embryoid bodies. Lab Invest. 1960 Nov-Dec;9:583–602. [PubMed] [Google Scholar]
  45. 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]
  46. PRICE J. M., HARMAN J. W., MILLER E. C., MILLER J. A. Progressive microscopic alterations in the livers of rats fed the hepatic carcinogens 3'-methyl-4-dimethylaminoazobenzene and 4'-fluoro-4-dimethylaminoazobenzene. Cancer Res. 1952 Mar;12(3):192–200. [PubMed] [Google Scholar]
  47. Papaioannou V. E., McBurney M. W., Gardner R. L., Evans M. J. Fate of teratocarcinoma cells injected into early mouse embryos. Nature. 1975 Nov 6;258(5530):70–73. doi: 10.1038/258070a0. [DOI] [PubMed] [Google Scholar]
  48. Peraino C., Fry R. J., Staffeldt E. Effects of varying the onset and duration of exposure to phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigenesis. Cancer Res. 1977 Oct;37(10):3623–3627. [PubMed] [Google Scholar]
  49. Peraino C., Fry R. J., Staffeldt E., Kisieleski W. E. Effects of varying the exposure to phenobarbital on its enhancement of 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res. 1973 Nov;33(11):2701–2705. [PubMed] [Google Scholar]
  50. Peraino C. Initiation and promotion of liver tumorigenesis. Natl Cancer Inst Monogr. 1981 Dec;(58):55–61. [PubMed] [Google Scholar]
  51. Petropoulos C. J., Yaswen P., Panzica M., Fausto N. Cell lineages in liver carcinogenesis: possible clues from studies of the distribution of alpha-fetoprotein RNA sequences in cell populations isolated from normal, regenerating, and preneoplastic rat livers. Cancer Res. 1985 Nov;45(11 Pt 2):5762–5768. [PubMed] [Google Scholar]
  52. Pierce G. B., Arechaga J., Jones A., Lewellyn A., Wells R. S. The fate of embryonal-carcinoma cells in mouse blastocysts. Differentiation. 1987;33(3):247–253. doi: 10.1111/j.1432-0436.1987.tb01564.x. [DOI] [PubMed] [Google Scholar]
  53. Pierce G. B., Wallace C. Differentiation of malignant to benign cells. Cancer Res. 1971 Feb;31(2):127–134. [PubMed] [Google Scholar]
  54. Pitot H. C. Endogenous carcinogenesis: the role of tumor promotion. Proc Soc Exp Biol Med. 1991 Nov;198(2):661–666. doi: 10.3181/00379727-198-43304. [DOI] [PubMed] [Google Scholar]
  55. Pitot H. C., Sirica A. E. The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta. 1980 May 6;605(2):191–215. doi: 10.1016/0304-419x(80)90004-9. [DOI] [PubMed] [Google Scholar]
  56. Potten C. S., Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990 Dec;110(4):1001–1020. doi: 10.1242/dev.110.4.1001. [DOI] [PubMed] [Google Scholar]
  57. Potten C. S., Schofield R., Lajtha L. G. A comparison of cell replacement in bone marrow, testis and three regions of surface epithelium. Biochim Biophys Acta. 1979 Aug 10;560(2):281–299. doi: 10.1016/0304-419x(79)90022-2. [DOI] [PubMed] [Google Scholar]
  58. Potter V. R. Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture. Br J Cancer. 1978 Jul;38(1):1–23. doi: 10.1038/bjc.1978.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rabes H. M., Wirsching R., Tuczek H. V., Iseler G. Analysis of cell cycle compartments of hepatocytes after partial hepatecomy. Cell Tissue Kinet. 1976 Nov;9(6):517–532. doi: 10.1111/j.1365-2184.1976.tb01301.x. [DOI] [PubMed] [Google Scholar]
  60. Rao M. S., Bendayan M., Kimbrough R. D., Reddy J. K. Characterization of pancreatic-type tissue in the liver of rat induced by polychlorinated biphenyls. J Histochem Cytochem. 1986 Feb;34(2):197–201. doi: 10.1177/34.2.2418098. [DOI] [PubMed] [Google Scholar]
  61. Rao M. S., Kokkinakis D. M., Subbarao V., Reddy J. K. Peroxisome proliferator-induced hepatocarcinogenesis: levels of activating and detoxifying enzymes in hepatocellular carcinomas induced by ciprofibrate. Carcinogenesis. 1987 Jan;8(1):19–23. doi: 10.1093/carcin/8.1.19. [DOI] [PubMed] [Google Scholar]
  62. Rao M. S., Lalwani N. D., Reddy J. K. Sequential histologic study of rat liver during peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]-acetic acid (Wy-14,643)-induced carcinogenesis. J Natl Cancer Inst. 1984 Oct;73(4):983–990. [PubMed] [Google Scholar]
  63. Rao M. S., Subbarao V., Reddy J. K. Peroxisome proliferator-induced hepatocarcinogenesis: histochemical analysis of ciprofibrate-induced preneoplastic and neoplastic lesions for gamma-glutamyl transpeptidase activity. J Natl Cancer Inst. 1986 Oct;77(4):951–956. [PubMed] [Google Scholar]
  64. Reddy J. K., Azarnoff D. L., Hignite C. E. Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature. 1980 Jan 24;283(5745):397–398. doi: 10.1038/283397a0. [DOI] [PubMed] [Google Scholar]
  65. Reddy J. K., Rao M. S., Azarnoff D. L., Sell S. Mitogenic and carcinogenic effects of a hypolipidemic peroxisome proliferator, [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14, 643), in rat and mouse liver. Cancer Res. 1979 Jan;39(1):152–161. [PubMed] [Google Scholar]
  66. Reddy J. K., Rao M. S., Qureshi S. A., Reddy M. K., Scarpelli D. G., Lalwani N. D. Induction and origin of hepatocytes in rat pancreas. J Cell Biol. 1984 Jun;98(6):2082–2090. doi: 10.1083/jcb.98.6.2082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. 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]
  68. Sarma D. S., Rao P. M., Rajalakshmi S. Liver tumour promotion by chemicals: models and mechanisms. Cancer Surv. 1986;5(4):781–798. [PubMed] [Google Scholar]
  69. Scarpelli D. G. Multipotent developmental capacity of cells in the adult animal. Lab Invest. 1985 Apr;52(4):331–333. [PubMed] [Google Scholar]
  70. Schulte-Hermann R. Tumor promotion in the liver. Arch Toxicol. 1985 Aug;57(3):147–158. doi: 10.1007/BF00290879. [DOI] [PubMed] [Google Scholar]
  71. Sell S., Becker F. F. alpha-Fetoprotein. J Natl Cancer Inst. 1978 Jan;60(1):19–26. doi: 10.1093/jnci/60.1.19. [DOI] [PubMed] [Google Scholar]
  72. 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]
  73. 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]
  74. Sell S., Dunsford H. A. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol. 1989 Jun;134(6):1347–1363. [PMC free article] [PubMed] [Google Scholar]
  75. 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]
  76. Sell S., Hunt J. M., Dunsford H. A., Chisari F. V. Synergy between hepatitis B virus expression and chemical hepatocarcinogens in transgenic mice. Cancer Res. 1991 Feb 15;51(4):1278–1285. [PubMed] [Google Scholar]
  77. Sell S., Hunt J. M., Knoll B. J., Dunsford H. A. Cellular events during hepatocarcinogenesis in rats and the question of premalignancy. Adv Cancer Res. 1987;48:37–111. doi: 10.1016/s0065-230x(08)60690-9. [DOI] [PubMed] [Google Scholar]
  78. Sell S. Is there a liver stem cell? Cancer Res. 1990 Jul 1;50(13):3811–3815. [PubMed] [Google Scholar]
  79. 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]
  80. Sell S., Sala-Trepat J. M., Sargent T. D., Thomas K., Nahon J. L., Goodman T. A., Bonner J. Molecular mechanisms of control of albumin and alphafetoprotein production: a system to study the early effects of chemical hepatocarcinogens. Cell Biol Int Rep. 1980 Mar;4(3):235–254. doi: 10.1016/0309-1651(80)90056-9. [DOI] [PubMed] [Google Scholar]
  81. 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]
  82. Shafritz D. A., Shouval D., Sherman H. I., Hadziyannis S. J., Kew M. C. Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. Studies in percutaneous liver biopsies and post-mortem tissue specimens. N Engl J Med. 1981 Oct 29;305(18):1067–1073. doi: 10.1056/NEJM198110293051807. [DOI] [PubMed] [Google Scholar]
  83. 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]
  84. 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]
  85. Shiojiri N., Lemire J. M., Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res. 1991 May 15;51(10):2611–2620. [PubMed] [Google Scholar]
  86. Sirica A. E., Mathis G. A., Sano N., Elmore L. W. Isolation, culture, and transplantation of intrahepatic biliary epithelial cells and oval cells. Pathobiology. 1990;58(1):44–64. doi: 10.1159/000163564. [DOI] [PubMed] [Google Scholar]
  87. Solt D. B., Medline A., Farber E. Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis. Am J Pathol. 1977 Sep;88(3):595–618. [PMC free article] [PubMed] [Google Scholar]
  88. 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]
  89. Stevens L. C. The development of transplantable teratocarcinomas from intratesticular grafts of pre- and postimplantation mouse embryos. Dev Biol. 1970 Mar;21(3):364–382. doi: 10.1016/0012-1606(70)90130-2. [DOI] [PubMed] [Google Scholar]
  90. Stocum D. L. The urodele limb regeneration blastema. Determination and organization of the morphogenetic field. Differentiation. 1984;27(1):13–28. doi: 10.1111/j.1432-0436.1984.tb01403.x. [DOI] [PubMed] [Google Scholar]
  91. Szmuness W. Hepatocellular carcinoma and the hepatitis B virus: evidence for a causal association. Prog Med Virol. 1978;24:40–69. [PubMed] [Google Scholar]
  92. 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]
  93. Teebor G. W., Becker F. F. Regression and persistence of hyperplastic hepatic nodules induced by N-2-Fluorenylacetamide and their relationship to hepatocarcinogenesis. Cancer Res. 1971 Jan;31(1):1–3. [PubMed] [Google Scholar]
  94. Tournier I., Legrès L., Schoevaert D., Feldmann G., Bernuau D. Cellular analysis of alpha-fetoprotein gene activation during carbon tetrachloride and D-galactosamine-induced acute liver injury in rats. Lab Invest. 1988 Nov;59(5):657–665. [PubMed] [Google Scholar]
  95. Van Duuren B. L., Sivak A., Katz C., Seidman I., Melchionne S. The effect of aging and interval between primary and secondary treatment in two-stage carcinogenesis on mouse skin. Cancer Res. 1975 Mar;35(3):502–505. [PubMed] [Google Scholar]
  96. Weinberg R. A. The action of oncogenes in the cytoplasm and nucleus. Science. 1985 Nov 15;230(4727):770–776. doi: 10.1126/science.2997917. [DOI] [PubMed] [Google Scholar]
  97. Yaswen P., Goyette M., Shank P. R., Fausto N. Expression of c-Ki-ras, c-Ha-ras, and c-myc in specific cell types during hepatocarcinogenesis. Mol Cell Biol. 1985 Apr;5(4):780–786. doi: 10.1128/mcb.5.4.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Zajicek G., Ariel I., Arber N. The streaming liver. III. Littoral cells accompany the streaming hepatocyte. Liver. 1988 Aug;8(4):213–218. doi: 10.1111/j.1600-0676.1988.tb00995.x. [DOI] [PubMed] [Google Scholar]
  99. Zajicek G., Oren R., Weinreb M., Jr The streaming liver. Liver. 1985 Dec;5(6):293–300. doi: 10.1111/j.1600-0676.1985.tb00252.x. [DOI] [PubMed] [Google Scholar]