EFFECTS OF INHIBITORS OF SPERMIDINE AND SPERMINE SYNTHESIS ON POLYAMINE CONCENTRATIONS AND GROWTH OF TRANSFORMED MOUSE FIBROBLASTS

The actions were investigated on cell [virally transformed mouse fibroblast SV-3T3 cells] growth and polyamine synthesis of a number of nucleosides [.alpha.-methylornithine, .alpha.-difluoromethylornithine, 1,1''-[(methylethanediylidene)dinitrilo]diguanidine and 1,1''-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine)] that have inhibitory actions in vitro against spermidine and spermine synthases. The availability of compounds that could block the polyamine biosynthetic pathway at the later steps catalyzed by these enzymes might be of value in the continued study of the role of individual polyamines in cellular proliferation. The effect of 5''-methylthioadenosine, the other product of the spermidine and spermine synthase reactions, was tested on cell growth and polyamine production. This nucleoside was a very potent inhibitor of the aminopropyltransferases, particularly spermine synthase. The presence of 5''-methylthioadenosine phosphorylase, which degrades this compound, may be esential to prevent its inhibitory properties becoming manifest, but the extent to which this enzyme acts in this way in vivo is not yet known.