Immunological study of carbon tetrachloride-mediated induction of tyrosine aminotransferase in rat liver

Abstract

Administration of CCl 4 (1.0 ml/kg) to rats resulted in a rise of liver tyrosine aminotransferase ( l-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) activity to a maximum of about 3.6 times the normal level 6 hr later. An immunological titration study proved that the phenomenon was due to increased enzyme content. Using an isotopic-immunochemical procedure the half-life of liver tyrosine aminotransferase at 3.5 hr after CCl 4 administration was shown to be 11.9 hr in contrast to 2.1 hr in the normal liver. Immunochemical analysis revealed that enzyme synthesis was decreased by CCl 4. Thus, in the early stage of CCl 4 poisoning, enzyme synthesis proceeded at a moderate rate while degradation was markedly impaired, resulting in the rise of tyrosine aminotransferase in the liver tissue. Several hours after administration of hydrocortisone to adrenalectomized rats, induced tyrosine aminotransferase reached its peak activity and then subsided to the basal level. At any time following hydrocortisone administration, administration of CCl 4 consistently caused an elevation of the enzyme activity above the level in controls not treated with CCl 4. Actinomycin D (5 mg/kg) also increased the enzyme at an early period of induction cycle but failed to do so at a later period. The CCl 4-mediated “superinduction” of hormonally preinduced tyrosine aminotransferase, like the induction of this enzyme by CCl 4 at a basal level, was found to be caused by the differential inhibitory effect of CCl 4 on the synthesis and degradation of this enzyme.