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Recent reports1 from this laboratory have established that the dietary induction of the hepatic enzymes serine dehydrase2 and ornithine a transaminase may be sensitive or insensitive to the action of the antibiotic actinomycin D, depending on the time at which the antibiotic is given relative to the administration of dietary protein. If actinomycin D, a potent inhibitor of template (messenger) RNA synthesis in mammalian cells,3 is administered during the initiation of induction, complete inhibition of enzyme synthesis results; but if the antibiotic administration is delayed until 12 hr after the induction is initiated, there is no significant effect on the rate of enzyme synthesis. A more extensive application of this basic procedure has made it possible to determine the length of time that the induction of serine dehydrase by casein hydrolysate remains insensitive to the action of actinomycin D. Since actinomycin D inhibits template RNA synthesis, then the template RNA for the enzyme serine dehydrase must be in a stable form capable of participating in protein synthesis for the duration of actinomycin insensitivity. On this basis the experiments reported herein are designed to determine the apparent lifetime of RNA templates in vivo, and present data which indicate the template lifetimes for several amino acid-catabolic enzymes in liver, and one enzyme in several hepatocellular carcinomas.

Template stability of some enzymes in rat liver and hepatoma.