INHIBITION OF CELL-GROWTH BY ACCUMULATED SPERMINE IS ASSOCIATED WITH A TRANSIENT ALTERATION OF CELL-CYCLE PROGRESSION

Exposure of HL-60 cells to millimolar levels of spermine resulted in t he inhibition of cell growth. Flow cytometry revealed that the additio n of exogenous spermine prevented the accumulation of cells in the S a nd G(2)/M phases of the cell cycle as observed in the control cells. H igh intracellular levels of spermine completely suppressed the early o nset of ornithine decarboxylase activity and, consequently, the intrac ellular increase in spermidine and putrescine. On the other hand, the addition of exogenous spermidine or putrescine also abolished ornithin e decarboxylase activity, but in this case neither the growth of sperm idine- or putrescine-treated cells nor the cell cycle phase distributi on was affected. In the latter cells, intracellular levels of spermidi ne were not significantly different from control ones. These results s uggest that the addition of exogenous spermine inhibits cell prolifera tion by hindering the increase in cellular spermidine needed to accele rate the G(1) to S phase transition.