Decreased protein-synthetic activity is an early consequence of spermidine depletion in rat hepatoma tissue-culture cells

Abstract

Hepatoma tissue-culture (HTC) cells were exposed to DL-alpha-difluoromethylornithine (DFMeOrn), a specific irreversible inhibitor of ornithine decarboxylase. Concomitantly with the decrease in spermidine, a decrease in the amount of ribosomes in polyribosomes was observed. Spermine concentrations remained essentially comparable with those in cells not exposed to this inhibitor. Exposure of putrescine- and spermidine-depleted HTC cells to spermidine or spermine rapidly reversed the effect of DFMeOrn on polyribosome profiles, whereas addition of putrescine to the cell culture medium had an effect only after its transformation into spermidine and spermine. The results show that the perturbation of polyribosome formation in DFMeOrn-treated HTC cells is due to spermidine deficiency and that a normal polyamine complement is required for optimal protein-synthetic activity in these cells. The results also indicate that protein synthesis is perturbed before DNA synthesis during depletion of putrescine and spermidine in HTC cells.