Inhibition of hepatic-induced enzyme formation by 8-azaguanine.

A body of evidence has accumulated which indicates that the :purine analogue, 8-azaguanine, has an inhibitory action upon protein synthesis. It has been shown in several laboratories that the production of certain inducible bacterial enzymes may be inhibited by this agent (14). It has also been reported by Mandel (5) that utilization of methionine-Ss5 and cystine-S35 for protein synthesis was markedly depressed in cultures of Bacillus cereus exposed to 8-azaguanine. Antibody production in the mouse may be suppressed by the administration of 8-azaguanine (6), and an effect upon hemoglobin synthesis in the deembryonated chick blastoderm has been noted (7). Although these studies point to an inhibition of protein synthesis as a possible major site of 8-azaguanine action they do not explain the mechanism by which inhibitions occur. These effects could be the result of a direct action on one or more of the biochemical mechanisms intimately involved in protein synthesis, or they could be merely a secondary phenomenon resulting from a more distant biochemical action, e.g. interference with a fundamental process such as phosphorylation, electron transport, amine acid metabolism, etc. To lay a proper foundation for the investigation of the mechanism in a cell-free system from rat liver, the effect of %aaaguanine upon the synthesis of several inducible hepatic enzymes in the rat was investigated.