Molecular Pharmacology, Vol 3, 1-8, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

Degradation of RNA in Liver of Rats Treated with Actinomycin D

¹ Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, New York

Actinomycin D (2 mg/kg) was given to rats after administration of a labeled RNA precursor (orotie-6-¹⁴C acid); thereafter, labeled RNA was extracted from nuclear and cytoplasmic fractions of liver and sedimented in sucrose gradients. Following treatment with actinomycin, newly synthesized RNA (i.e., labeled 40 min or less before the drug was given) was lost labeled RNA failed to appear in the cytoplasm. This loss also occurred in adrenalectomized mats. There was no apparent loss of older RNA (i.e., labeled 3 hr before drug) or massive destruction of unlabeled ribosomes amid polysomes. The results suggest that time transfer of labeled RNA from the nucleus to the cytoplasm was blocked because of destruction of precursors of ribosomal RNA. Since these and other forms of RNA are synthesized in the nucleus, it is likely that the loss occurred here, possibly at nucleolar sites which are thought to participate in ribosomnal synthesis.

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ACKNOWLEDGMENTS The authors express gratitude to Miss Dionne Bolling for willing assistance in some of these experiments, to Dr. Emmanuel Farber for helpful discussions and suggestions, and to Dr. Frederick S. Philips for invaluable assistance in the preparation of this manuscript. This research was supported by Grants CA-03192 and CA-08748 from the National Cancer Institute, United States Public Health Service.