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Studies on the Relationship between Increased Adenylic Acid Deaminase Activity and Changes in Nuclear RNA Metabolism in Rat Liver Caused by Thioacetamide

Biomedical Division, The Samuel Roberts Noble Foundation, Inc., Ardmore, Oklahoma

The purpose of this study was to determine whether increases in AMP¹ 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 NNN² or "nucleolar" RNA, and incorporation of orotic acid-6-¹⁴C 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-6-¹⁴C 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.

¹ The abbreviations used are: AMP, adenylic acid; TA, thioacetamide; Act. D, actinomycin D; 5-FU, 5-fluorouracil; ATP, adenosine triphosphate; 3'-Me-DAB, 3'-methyl-4-dimethylaminoazobenzene; and IMP, inosinic acid.

² "NNN" (nonnucleolar nuclear) and "nucleolar" were terms used by Koulish and Kleinfeld (18) to designate cytologically distinct portions of nuclear RNA. Here, "NNN" indicates the phosphate buffer-soluble fraction, while "nucleolar" indicates the 1 M NaCl-insoluble fraction of the Allfrey and Mirsky (1) subfractionation procedure. We have previously discussed the relationship of our NNN fraction to "nonnucleolar" nuclear RNA, and cytologic limitations have been recognized (17).

Received 11/17/65.