Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM-26, VP-16-213) on the cell cycle traverse of human lymphoblasts

Flow microfluorometric analysis of human lymphoid cells exposed in vitro to cytostatic concentrations of podophyllotoxin (0.01-5 µg/ml for 24 h) shows that a major part of this population (40-60%) has the DNA content of cells in the G₂-M part of the cell cycle, and that approximately 60% of these cells are arrested in mitosis. Although a similar pattern of DNA distribution is seen in cultures exposed to cytostatic concentrations of VM-26 (0.01 µg/ml) and VP-16-213 (0.1 µg/ml), no mitotic cells are seen in these cultures. Exposure to higher concentrations of VM-26 (0.1 g/ml) and VP-16-213 (1.0 µg/ml) inhibits cell cycle traverse, and after 24 h of exposure a major part of the population is arrested with the DNA content of cells in the S part of the cell cycle. Exposure to higher drug concentrations leads to a reduction in the number of cells with the late S-G2 DNA content. Whereas the cell cycle block induced by cytostatic concentrations of podophyllotoxin (0.01 µg/ml) is readily reversible by reincubation of cells in drug-free medium, cells blocked by VM-26 and VP-16-213 are unable to resume cell-cycle traverse under similar conditions.