[Functional activity of fractionated chromatin from rat liver upon a single administration of carbon tetrachloride]

Abstract

Functions of rat liver cell genome were distinctly altered after a single administration of tetrachloromethane into animals. Maximal alterations in the structure-functional properties of chromatin were detected within 2 hrs after intoxication. The phenomenon was accompanied by the following shifts in the chromatin active fractions: activation of DNA- and RNA polymerases, decrease in content of this fraction, increase in the ratio protein/DNA due to elevation in the protein component with molecular mass 65 kDa detected in the nonhistone fraction of electrophoretogram. Alterations in the repressed chromatin fraction were less distinct. Many parameters of the chromatin fractions were normalized within 24 hrs after the intoxication. Peroxidation of lipids contained in chromatin occurred via NADPH-and ascorbate-dependent reactions, the rate of which was distinctly higher in the repressed chromatin fraction of liver cells from the animals intoxicated within 24 hrs. These alterations in the structure-functional properties of liver chromatin fractions, developed after a single administration of tetrachloromethane into animals, were related neither to the rate of lipid peroxidation in chromatin, stimulated by tetrachloromethane, nor to alterations in Ca2+ and Mg2+ content in nuclear fraction. cAMP-dependent phosphorylation of chromatin proteins appears to be rather responsible for chemical impairments of hepatocyte membranes stimulated by tetrachloromethane.