Skip to main content
Log in

Chromosomal proteins in hepatocarcinogenesis

  • Original Papers
  • Published:
Zeitschrift für Krebsforschung und Klinische Onkologie Aims and scope Submit manuscript

Summary

The chromosomal proteins of rat liver were studied by SDS-gel electrophoresis during the process of nitrosomorpholine-induced hepatocarcinogenesis, in the primary hepatomas thus obtained, and in their metastases. It was found that an increased proteolytic activity was present in liver homogenates from carcinogen-fed animals which caused differences between the nonhistone chromosomal proteins of control and carcinogen-treated livers. These differences disappeared in the presence of the protease inhibitor PMSF.

In the primary hepatomas slight quantitative changes were observed: an increased amount of two proteins of 43000 and 63000 daltons molecular weight, respectively, and a decrease in the histone subfraction H 1°. In the metastases both quantitative and qualitative differences were detected: a strong decrease in the protein bands corresponding to the contractile proteins α-tubulin, β-tubulin, and actin; an increased content of the 63000 dalton protein; the appearance of new proteins of approximately 60000, 90000, and 120000 daltons molecular weight, and the complete disappearance of histone H1°.

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. Alonso,A., Arnold,H.P.: Stimulation of amino acids incorporation into rat liver nonhistone chromatin proteins after treatment with diethylnitrosamine. FEBS Letters 41, 8–10 (1974)

    Google Scholar 

  2. Anachkova,B., Russev,G., Tsanev,R.: Comparative study of the nonhistone chromosomal proteins of rat liver, thymus and brain. Int. J. Biochem. 8, 135–139 (1977)

    Google Scholar 

  3. Arnold,E.A., Buksas,M.M., Young,K.E.: A comparative study of some properties of chromatin from two minimal deviation hepatomas. Cancer Res. 33, 1169–1176 (1973)

    Google Scholar 

  4. Augenlicht,L.H., Biessmann,H., Rajewsky,M.F.: Chromosomal proteins of rat brain: increased synthesis and affinity for DNA following a pulse of the carcinogen ethylnitrosourea in vivo. J. Cell. Physiol. 86, 431–438 (1975)

    Google Scholar 

  5. Balhorn,R., Chalkley,R., Granner,D.: Lysine-rich histone phosphorylation. A positive correlation with cell replication. Biochemistry 11, 1094–1098 (1972)

    Google Scholar 

  6. Baserga,R.: Non-histone chromosomal proteins in normal and abnormal growth. Life Sciences 15, 1057–1071(1974)

    Google Scholar 

  7. Baserga,R., Nicolini,C.: Chromatin structure and function in proliferating cells. Biochim. Biophys. Acta 458, 109–134 (1976)

    Google Scholar 

  8. Biesmann,H., Rajewsky,M. F.: Nuclear protein pattern in developing and adult brain in ethylnitrosourea-induced neuroectodermal tumors of the rat. J. Neurochem. 24, 387–393 (1975)

    Google Scholar 

  9. Botta,L.C., Vidali,G., Allfrey,V.G.: Changes in nuclear nonhistone protein composition during normal differentiation and carcinogenesis of intestinal epithelial cells. Exp. Cell Res. 98, 396–410 (1976)

    Google Scholar 

  10. Bucher,N.L.R., Malt,R.A.: Regeneration of liver and kidney. Boston: Little, Brown and Co. (1971)

    Google Scholar 

  11. Chae,C.B., Smith,M.C, Morris,H.P.: Chromosomal nonhistone proteins of rat hepatomas and normal rat liver. Biochem. Biophys. Res. Commun. 60,1468–1474 (1974)

    Google Scholar 

  12. Chin,J.F., Craddock,C., Morris,H.P., Hnilica,L.S.: Immunospecificity of chromatin nonhistone protein-DNA complexes in normal and neoplastic growth. FEBS Letters 42, 94–97 (1974)

    Google Scholar 

  13. Chin,J.F., Hunt,M., Hnilica,L.S.: Tissue specific DNA-protein complexes during azo dye hepatocarcinogenesis. Cancer Res. 35, 913–919 (1975)

    Google Scholar 

  14. Comings,D.E., Harris,D.: Nuclear proteins. II. Similarity of nonhistone proteins in nuclear sap and chromatin and essential absence of contactile proteins from mouse liver nuclei. J. Cell Biol. 70, 440–452 (1976)

    Google Scholar 

  15. Cooper,H.K., Itzhaki,R.F.: Studies on liver chromatin from rats treated with dimethylnitrosamine. Biochim. Biophys. Acta 407, 263–272 (1975)

    Google Scholar 

  16. Douvas,A.S., Harrington,C.A., Bonner,J.: Major nonhistone proteins of rat liver chromatin: Preliminary identification of myosin, actin, tubulin and tropomyosin. Proc. Natl. Acad. Sci. USA 72, 3902–3906 (1975)

    Google Scholar 

  17. Druckrey,H., Preussmann,R., Ivankovic,S., Schmähl,D.: Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitrosoverbindungen an BD-Ratten. Z. Krebsforsch. 69, 103–201 (1967)

    Google Scholar 

  18. Elgin,S.C.R., Bonner J.: Partial fractionation and chemical characterization of the major nonhistone chromosomal proteins. Biochemistry 11, 772–781 (1972)

    Google Scholar 

  19. Fahrney,D., Gold,A.: Sulfonylfluorides as inhibitors of esterases. I. Rates of reaction with acetylcholinesterase, α-chymotrypsin and trypsin. J. Am. Chem. Soc. 85, 997–1000 (1963)

    Google Scholar 

  20. Forger III,J.M., Choie,D.D., Friedberg,E.C.: Nonhistone chromosomal proteins of chemically transformed neoplastic cells in tissue culture. Cancer Res. 36, 258–262 (1976)

    Google Scholar 

  21. Fujitani,H., Holoubek,V.: Nuclear proteins of rat liver and of an aminoazo-dye-induced hepatoma. Int. J. Cancer 16, 329–338 (1975)

    Google Scholar 

  22. Gronow,M.: Changes in rat liver nonhistone nuclear proteins during nitrosamine carcinogenesis. Biochem. J. 124, 49 p. (1971)

    Google Scholar 

  23. Gronow,M., Thackrah,T.M.: Nuclear protein changes during nitrosamine-induced carcinogenesis of rat liver. Chem. Biol. Interactions 9, 225–236 (1974)

    Google Scholar 

  24. Hadjiolov,D., Markov,D.: Effect of aminoacetonitrile on the fine structure and cytochemistry of hepatic cells in rats fed two carcinogenic N-nitrosodialkylamines. J. Natl. Cancer Inst. 50, 979–988 (1973)

    Google Scholar 

  25. Johns,E.W., Forrester,S.: Studies on nuclear proteins. Eur. J. Biochem. 8, 547–551 (1969)

    Google Scholar 

  26. Kadohama,N., Turkington,R.W.: Altered population of acidic chromatin proteins in breast cancer cells. Cancer Res. 33, 1194–1201 (1973)

    Google Scholar 

  27. Kinkade,J.M., Jr.: Differences in the quantitative distribution of lysine-rich histones in neoplastic and normal tissues. Proc. Soc. Exp. Biol. Med., N. Y. 137, 1131–1134 (1971)

    Google Scholar 

  28. Laemmli,U.K.: Clevage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 608–685 (1970)

    Google Scholar 

  29. Lea,M.A., Youngworth,L.A., Morris,H.P.: Acid soluble nuclear proteins of rat liver: differential absorbance of bound dyes and changes in neoplasia. Biochem. Biophys. Res. Commun. 85, 862–867 (1974)

    Google Scholar 

  30. Lea,M.A., Koch,M.R., Morris,H.P.: Nuclear protein changes in rat hepatomas correlating with growth rate. Cancer Res. 35, 1693–1697 (1975)

    Google Scholar 

  31. Lestourgeon,W.M., Forer,A., Yang,Y.Z., Bertram,J., Rusch,H.P.: Contractile proteins. Biochim. Biphys. Acta 379, 529–552 (1975)

    Google Scholar 

  32. Marks,D.B., Kanetsky,T., Keller,B.J., Marks,A.D.: The presence of histone H 1° in human tissues. Cancer Res. 35, 886–889 (1975)

    Google Scholar 

  33. Warsh,W.H., Fitzgerald,P.J.: Pancreas acinar regeneration. XIII. Histone synthesis and modification. Federation Proc. 32, 2119–2125 (1973)

    Google Scholar 

  34. Orrick,L.R., Olson,M.O.J., Busch,H.: Comparison of nucleolar proteins of normal rat liver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Proc. Natl. Acad. Sci. USA, 70, 1316–1320 (1973)

    Google Scholar 

  35. Panyim,S., Jensen,R.H., Chalkley,R.: Proteolytic contamination of calf thymus nucleohistone and its inhibition. Biochim. Biphys. Acta 160, 252–255 (1968)

    Google Scholar 

  36. Panyim,S., Chalkley,R.: A new histone found only in mammalian tissues with little cell divisions. Biochem. Biophys. Res. Commun. 37, 1042–1049 (1969)

    Google Scholar 

  37. Peterson,J.L., McConkey,E.H.: Proteins of Friend leukemia cells. J. Biol. Chem. 251, 555–558 (1976)

    Google Scholar 

  38. Russev,G., Anachkova,B., Tsanev,R.: Fractionation of rat liver chromatin nonhistone proteins into two groups with different metabolic rates. Eur. J. Biochem. 58, 253–257 (1975)

    Google Scholar 

  39. Selgen,P.O.: The use of metrizamide for the separation of rat liver cells. In: Biological separations in iodinated density gradient media (Rickwood,D., ed.). London and Washington: IRL 1976

    Google Scholar 

  40. Sluyser,M., Bustin,M.: Immunological specificities of lysine-rich histones from tumors. J. Biol. Chem. 249, 2507–2511 (1974)

    Google Scholar 

  41. Stein,G.S., Spelsberg,T.C., Kleinsmith,L.J.: Nonhistone chromosomal proteins and gene regulation. Science 183, 817–824 (1974a)

    Google Scholar 

  42. Stein,G.S., Criss,W.E., Morris,H.P.: Properties of the genome in experimental hepatomas: variations in the composition of chromatin. Life Sci. 14, 95–105 (1974b)

    Google Scholar 

  43. Tsanev,R., Sendov,B.: Possible molecular mechanism for cell differentiation in multicellular organisms. J. Theoret. Biol. 30, 337–393 (1971a)

    Google Scholar 

  44. Tsanev,R., Sendov,B.: An epigenetic mechanism for carcinogenesis. Z. Krebsforsch. 76, 299–319 (1971b)

    Google Scholar 

  45. Tsanev,R., Russev,G.: Distribution of newly sythesized histones during DNA replication. Eur. J. Biochem. 43, 257–263 (1974)

    Google Scholar 

  46. Tsanev,R.: Cellular differentiation and the structure of chromatin. Proc. 9th FEBS Meeting 33, 409–417 (1975)

    Google Scholar 

  47. Wakabayashi,K., Hnilica,L.S.: The immunospecificity of nonhistone protein complexes with DNA. Nature New Biol. 242, 153–155 (1973)

    Google Scholar 

  48. Weisenthal,L.M., Ruddon,R.W.: Catabolism of nuclear proteins in control and PHA-stimulated human lyphocytes, leukemic leukocytes and Burkitt lymphoma cells. Cancer Res. 33, 2923–2935 (1973)

    Google Scholar 

  49. Weisenthal,L.M., Ruddon,R.W.: Characterization of human leukemia and Burkitt lymphoma cells by their acidic nuclear proteins. Cancer Res. 32, 1009–1017 (1972)

    Google Scholar 

  50. Wilson,B., Lea,M., Vidali,G., Allfrey,V.G.: Fractionation of nuclei and analysis of nuclear proteins of rat liver and Morris hepatoma 7777. Cancer Res. 35, 2954–2958 (1975)

    Google Scholar 

  51. Yeoman,L.C., Taylor,C.W., Jordan,J.J., Busch,H.: Two-dimensional polyacrylamide gel electrophoresis of chromatin proteins of normal rat liver and Novikoff hepatoma ascites cells. Biochem. Biophys. Res. Commun. 53, 1067–1076 (1976)

    Google Scholar 

  52. Yeoman,L.C., Taylor,C., Jordan,J.J., Busch,H.: Early and late changes in nonhistone chromatin proteins accompanying rat liver regeneration. Cancer Res. 35, 1249–1255 (1975)

    Google Scholar 

  53. Zardi,L., Lin,J.C., Baserga,R.: Immunospecificity to nonhistone chromosomal proteins of antichromatin antibodies. Nature New Biol. 245, 211–213 (1973)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsanev, R., Hadjiolov, D. Chromosomal proteins in hepatocarcinogenesis. Z. Krebsforsch. 91, 237–247 (1978). https://doi.org/10.1007/BF00312286

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00312286

Keywords

Navigation