Abstract

The effects of actinomycin-D and 3'-deoxyadenosine (cordycepin) on the steroid-mediated induction of tyrosine aminotransferase (TAT) synthesis have been reexamined in view of recent reports that the primary inhibitory action of these compounds may affect synthesis of proteins as well as RNA. The present results confirm that cordycepin blocks the steroid-mediated induction of TAT in rat hepatoma cells (HTC), but unlike actinomycin-D, cordycepin neither increases nor maintains the levels of TAT found in HTC cells preinduced with dexamethasone. Indeed, cordycepin added to preinduced cells, either in the presence or absence of steroid, causes a prompt decline in TAT activity. These data also confirm that both actinomycin-D and cordycepin have an early inhibitory effect on protein synthesis, but the cordycepin effect is observed sooner and the extent of inhibition is greater. When actinomycin-D and cordycepin are added simultaneously to preinduced cells with the steroid removed, the actinomycin-td produced maintenance of preinduced levels of TAT persists. Also, the inhibition of protein synthesis in cultures with both inhibitors approaches that for the cells treated with actinomycin-D alone instead of cordycepin alone. These data suggest that cordycepin inhibits TAT synthesis in preinduced cells by its inhibition of protein synthesis, and this inhibitory effect of cordycepin is blocked by actinomycin-D. It is possible that actinomycin-D does this by preventing the incorporation of cordycepin into RNA. However, regardless of the correctness of this speculation, the multiple effects of cordycepin indicate that this inhibitor cannot be used either to prove or rule out the post-transcriptional model for regulation of gene expression. Also, this requirement that protein synthesis must continue in order to maintain pre-induced levels of TAT is inconsistent with the assumption that the maintenance of these induced TAT levels by actinomycin-D is due to inhibition of TAT degradation.

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