Cell cycle stage-dependent induction of G₂ phase arrest by different antitumor agents

A variety of chemically unrelated antitumour compounds has been shown to block cell cycle progression in G₂ phase. Using thymidine synchronized human lymphoid cells, we have investigated the cycle stage dependency of this kinetic response. For anthracycline antibiotics (adriamycin, adriamycin-DNA complex and rubidazone) and the epipodophyllotoxin derivative VP16, cells in S phase were most susceptible to the induction of G₂ block in the immediate life span. Alkylating agents (melphalan, peptichemio and Toshi 864) displayed a peculiar sensitivity pattern: G₁ cells were effectively delayed in the subsequent G₂ phase, whereas this kinetic event was transmitted to the daughter cell population when treatment was commenced in G₂ phase. The time of manifestation of G₂ block after incubation in S phase varied among the three alkylating agents and was a function of the position in S phase. In general, there was no correlation between phase sensitivity for induction of G₂ block and lethal cell damage.