Effects of ledakrin on DNA and cell cycle in HeLa S3 cells.

An antitumour DNA cross-linking drug, ledakrin, and other antitumour 1-nitro-9-aminoacridines applied to HeLa S3 cells caused a preferential accumulation of cells in S phase, as found by the flow cytometry technique. At lower drug levels, this effect was partially reversed upon prolonged incubation. In contrast, no recovery of the distribution of the cells in the various cell cycle phases was observed with higher ledakrin concentrations (7.4 nM and higher). The action of the drug at higher concentrations also resulted in strong lysis of HeLa S3 cells. The results obtained are consistent with ledakrin's ability to block DNA replication in HeLa S3 cells by inhibiting the rate of chain growth. However, the actual role of the S phase block in the antiproliferative action of 1-nitro-9-aminoacridines is not unequivocal, since the lysis observed might preferentially concern the cells in one particular phase, thereby concealing a block in a phase other than the S phase of the cell cycle.