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Tissue-specific DNA-Protein Complexes during Azo Dye Hepatocarcinogenesis¹

Department of Biochemistry, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77025

The administration of a carcinogen, N,N-dimethyl-p-(m-tolylazo)aniline, to Fischer rats changed the immunological specificity of the chromosomal nonhistone protein complexes with DNA of the same species (homologous) from the type characteristic of normal tissue (liver) to a new type, common to several experimental tumors, including hepatomas. This change in immunospecificity paralleled, to some extent, the increase of the ₁-fetoprotein in sera of the experimental animals.

Using in vitro reconstitution of chromatin protein fractions, it was shown that the immunological tissue specificity of chromatin protein:DNA complexes depends on the presence of a protein fraction that binds only to homologous DNA. The immunological tissue specificity could be transferred from one chromatin preparation to another by reconstituting this protein fraction to the DNA and the remaining chromatin components.

¹ Supported by NIH Contract NO1 CP 43270. A preliminary report of this work was presented at the Ciba Foundation Symposium on the Structure and Function of Chromatin, London, 1974.

Received 9/30/74. Accepted 12/16/74.