The Molecular Toxicology of Chromatin.
Annual rept. 1 Oct 82-30 Sep 83,
CALIFORNIA UNIV SAN FRANCISCO DEPT OF PHARMACOLOGY
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The chemical macromolecular structure and biological function of the eukaryotic cell specific nuclear polymer polyadenosine diphosphoribose has been investigated in specific cell nuclei isolated from animals rats and from human fibroblast cultures. This polymer is formed enzymatically from NAD in eukaryotic nuclei. The polymer was identified for the first time, as a unique nucleic acid structure which can form helix-helix type non-covalent association between long chain polymers that are on one end covalently bound to non histone proteins, comprising a supramolecular DNA structure associated network system. The influence of differentiation determined by assays in different cell types within one organ and effects of developmental hormones in animals on polyadenosine diphosphoribosylation and the role of the polymer in cell transformation in cell cultures has been studied by focusing on the quantitative and qualitative changes of non histone protein-polyadenosine diphosphoribose adducts in chromatin under controlled experimental conditions. A positive correlation was found between changes inhibition in rates of polyadenosine diphosphoribosylation and cellular hypertrophy of cells incapable of DNA synthesis indicating a physiologic control function of the polymer-protein network system in DNA template activity in these cells.