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A new nucleosomal protein in normal liver related to the cytoplasmic polypeptide target of a carcinogen

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Summary

Normal adult rat liver contains a nucleosomal protein that is related to the principal target polypeptide of a carcinogen in cytoplasm. Normal rat liver was found previously to contain a 14 000-dalton polypeptide that is the principal. cytosolic target of the carcinogen, N-2-fluorenylacetamide (2-acetylaminofluorene; FAA), early during hepatocarcinogenesis. Elevated levels of immunohistochemically detectable target polypeptide in cytoplasm are associated with normal mitosis and carcinogen-induced hyperplasias in adult hepatocytes. A putatively related 17 500-dalton polypeptide was shown to be tightly bound to chromatin of normal liver nuclei. We report here that purified nucleosomes from normal rat liver contain the bound 17 500-dalton protein. Nuclei were digested with micrococcal nuclease, and the resultant nucleosomes were resolved into size classes by density gradient sedimentation. The monomers, dimers, and trimers of nucleosomes possessed bound 17 5019-dalton polypeptide, as determined by SDS gel electrophoresis followed by immunoelectroblot analyses. Alterations in the levels of the two polypeptides were shown previously to occur during liver carcinogenesis by FAA and 3′-methyl-4-dimethylaminoazobenzene. The findings support the possibility that the 17 500-dalton polypeptide may function normally in a role related to the replication or expression of the hepatic genome, and may be connected with changes in hepatic genic activity brought about by the carcinogens.

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Abbreviations

FAA:

N-2-fluorenylacetamide (2-acetylaminofluorene)

3′-Me-DAB:

3′-methyl-4-dimethylaminoazobenzene

EDTA:

ethylenediaminetetraacetic acid

SDS:

sodium dodecyl sulfate

References

  1. Blackburn GR, Andrews JP, Rao RVK, Sorof S: An early event associated with liver carcinogenesis involving loss of a polypeptide that binds carcinogen. Cancer Res 40:4688–4693, 1980.

    Google Scholar 

  2. Blackburn GR, Andrews JP, Custer RP, Sorof S: Early events during liver carcinogenesis involving two carcinogen: protein complexes. Cancer Res 41:4039–4049, 1981.

    Google Scholar 

  3. Blackburn GR, Schnabel SJ, Danley JM, Hogue-Angeletti RA, Sorof S: Principal polypeptide target of carcinogen at the beginning of liver carcinogenesis by three carcinogens. Cancer Res 42:4664–4672, 1982.

    Google Scholar 

  4. Vinores SA, Churey JJ, Haller JM, Schnabel SJ, Custer RP, Sorof S: Normal liver chromatin contains a firmly bound and larger protein related to the principal cytosolic target polypeptide of a hepatic carcinogen. Proc Natl Acad Sci USA 81: 2092–2096, 1984.

    Google Scholar 

  5. Custer RP, Sorof S: Target polypeptide of a carcinogen is associated with normal mitosis and carcinogen-induced hyperplasias in adult hepatocytes. Proc Natl Acad Sci USA 81:6738–6742, 1984.

    Google Scholar 

  6. Miller EC, Miller JA: Mechanisms of chemical carcinogenesis. Cancer 47:1055–1064, 1981.

    Google Scholar 

  7. Miller EC, Miller JA: Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules. Cancer 47:2327–2345, 1981.

    Google Scholar 

  8. Farber E: Cellular biochemistry of the sequential development of cancer with chemicals: GHA Clowes Memorial Lecture. Cancer Res 44:5463–5474. 1984.

    Google Scholar 

  9. Grisham JW: Cellular proliferaton in the liver. Recent Results in Cancer Res 17:28–43, 1969.

    Google Scholar 

  10. Farber E, Cameron R: The sequential analysis of cancer development. Adv Cancer Res 31:125–226, 1980.

    Google Scholar 

  11. Noll M: Subunit structure of chromatin. Nature 251:249–251, 1974.

    Google Scholar 

  12. Levinger L, Varshavsky A: High-resolution fractionation of nucleosomes: Minor particles, ‘whiskers’, and separation of mononucleosomes containing and lacking A24 semhistone. Proc Natl Acad Sci USA 77:3244–3248, 1980.

    Google Scholar 

  13. Olins AL, Carlson RD, Wright EB, Olins DE: Chromatin v bodies: isolation, subfractionation and physical characterization. Nucleic Acids Res 3:3271–3291, 1976.

    Google Scholar 

  14. Bakayev VV, Bakayeva TG, Varshavsky AJ: Nucleosomes and subnucleosomes: heterogeneity and composition. Cell 11:619–629, 1977.

    Google Scholar 

  15. Todd RD, Garrard WT: Two-dimensional electrophoretic analysis of polynucleosomes. J Biol Chem 252:4729–4738, 1977.

    Google Scholar 

  16. Igo-Kemenes T, Horz W, Zachau HG: Chromatin. Ann Rev Biochem 51:89–121, 1982.

    Google Scholar 

  17. Yankner BA, Shooter EM: Nerve growth factor in the nucleus: Interaction with receptors on the nuclear membrane. Proc Natl Acad Sci USA 76:1269–1273, 1979.

    Google Scholar 

  18. Vanderbilt JN, Bloom KS, Anderson JN: Endogenous nuclease. Properties and effects on transcribed genes in chromatin. J Biol Chem 257:13009–13017, 1982.

    Google Scholar 

  19. Laemmli UK: Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227:680–685, 1970.

    PubMed  Google Scholar 

  20. Wray W, Boulikas T, Wray VP, Hancock R: Silver staining of proteins in polyacrylamide gels. Anal Biochem 118: 197–203, 1981.

    CAS  PubMed  Google Scholar 

  21. Solt DB, 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 88: 595–618, 1977.

    Google Scholar 

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Authors and Affiliations

  1. Fox Chase Cancer Center, Institute for Cancer Research, 19111, Philadelphia, PA, USA

    James A. Bassuk & Sam Sorof

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  1. James A. Bassuk
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  2. Sam Sorof
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Bassuk, J.A., Sorof, S. A new nucleosomal protein in normal liver related to the cytoplasmic polypeptide target of a carcinogen. Mol Cell Biochem 68, 49–57 (1985). https://doi.org/10.1007/BF00219388

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  • DOI: https://doi.org/10.1007/BF00219388

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