A Study of the Mechanism of Polyribosome Breakdown Induced in Regenerating Liver by 8-Azaguanine

Following the administration of 8-azaguanine to rats, a portion of the polyribosomes in regenerating liver are converted to monomers and dimers, with a concomitant inhibition of protein synthesis. Polyribosome breakdown induced by suboptimal doses of the base analogue and the incorporation of 8-azaguanine-14C into RNA are enhanced by pretreating the rats with low doses of 4-amino-5-imidazolecarboxamide. The dimers are labile, and break down to monomers after a short incubation at 37°. The monomer and dimer pool appears to be nonfunctional in vivo; only the residual polyribosomes are pulse labeled with l-leucine-14C. The latter finding suggests that the former species did not originate from breakdown of the latter species during isolation. The residual polyribosomes incorporated l-leucine-14C in vivo at rates comparable to those of polyribosomes in controls. The data are consistent with the incorporation of 8-azaguanine into certain species of RNA, probably messenger RNA, which are essential to the integrity of the polyribosome.