Studies on the relationship between increased adenylic acid deaminase activity and changes in nuclear RNA metabolism in rat liver caused by thioacetamide.

Abstract

Summary The purpose of this study was to determine whether increases in AMP 1 deaminase activity caused by TA injections were mediated by RNA biosynthesis. Multiple TA injections (50 mg/kg body weight) resulted in 2- to 3-fold increases in AMP deaminase activity, but simultaneous injection of Act. D (120 µg/kg body weight) or 5-FU (30 mg/kg body weight) with TA caused no interference with this increase. AMP deaminase was activated in vitro with ATP; however, in the presence of ATP the enzyme activity of TA-injected animals was twice that of saline controls, and these increases still were not inhibited by Act. D or 5-FU. On the other hand, Act. D inhibited, but 5-FU enhanced, the increases in nucleoli diameters caused by TA injections. Neither 1 nor 4 injections of Act. D alone changed the concentration of NNN 2 or “nucleolar” RNA, and incorporation of orotic acid-6- 14 C into these fractions was not altered. When Act. D was injected simultaneously with TA, it did not inhibit increases in “nucleolar” RNA content nor increases in the incorporation of labeled orotic acid into the NNN fraction. Single injections of Act. D at 650 µg/kg body weight, alone or with TA, inhibited incorporation of orotic acid-6- 14 C into both NNN and “nucleolar” RNA about 50%. This high level of Act. D was divided into 18 doses and injected at 4-hr intervals over a 3-day period to TA-treated rats. Increases in AMP deaminase activity were not inhibited, but incorporation of labeled orotic acid was inhibited.