Cycle-Dependent Anticancer Drug Cytotoxicity in Mammalian Cells Synchronized by Centrifugal Elutriation2

Abstract

The cycle-dependent cytotoxicity of seven chemotherapy agents was compared with the use of subpopulations of Chinese hamster ovary cells separated into the various phases of the cell cycle by centrifugal elutriation. The proportion of cells killed by either β-cytosine arabinoslde or hydroxyurea agreed well with the proportion of S-phase cells in the treated subpopulations. Cell-cycle survival patterns were also determined for bleomycin (BLM), adriamycln (ADR), c/s-diamminedichloroplatinum (II) (c/s-DDP), Asaley, and Yoshi 864. Three of the agents (c/s-DDP, Asaley, and Yoshi 864) had similar cell-cycle survival patterns in that they all preferentially killed cells in the G₁ phase. In contrast, BLM preferentially killed cells in G₂+M phase, whereas ADR was most cytotoxic to cells in middle to late Sphase. This investigation demonstrated that separation of cultured mammalian cells into the various cell-cycle phases by centrifugal elutriation allows the rapid determination of the phase-dependent cytotoxic effects exerted by chemotherapy agents.