Treatment of cells with the polyamine analog N-1,N-11-diethylnorspermine retards S phase progression within one cell cycle

When Chinese hamster ovary cells were seeded in the presence of the spermin e analog N-1,N-11-diethylnorspermine (DENSPM), cell proliferation ceased; t his was clearly apparent by cell counting 2 days after seeding the cells. H owever, 1 day after seeding there was a slight difference in cell number be tween control and DENSPM-treated cultures. To investigate the reason for th is easily surpassed slight difference, we used a sensitive bromodeoxyuridin e/flow cytometry method. Cell cycle kinetics were studied during the first cell cycle after seeding cells in the absence or presence of DENSPM. Our re sults show that DENSPM treatment did not affect the progression of the cell s through G(1) or the first G(1)/S transition that took place after seeding the cells. The first cell cycle effect was a delay in S phase as shown by an increase in the DNA synthesis time. The following G(2)/M transition was not affected by DENSPM treatment. DENSPM treatment inhibited the transient increases in putrescine, spermidine, and spermine pools that took place wit hin 24 h after seeding. Thus, in conclusion, the first cell cycle phase aff ected by the inhibition of polyamine biosynthesis caused by DENSPM was the S phase. Prolongation of the other cell cycle phases occurred at later time points, and the G(1) phase was affected before the G(2)/M phase.