LIFE, DEATH AND GENOMIC CHANGE IN PERTURBED CELL-CYCLES

HeLaS3 cells undergo apoptosis after 18-24h of cell cycle stasis irres pective of the agent employed (colcemid, aphidicolin, cis-platin). At high drug concentrations apoptosis occurs in cells arrested in the cel l cycle in which the drug is applied and at a cell cycle position depe ndent on the mechanism of drug action. At low concentrations (or short exposure times) cells undergo apoptosis after progressing through an aberrant mitosis and only after 18 h of cell cycle stasis in a 'pseudo G1/S' cell cycle position. Aberrent mitoses result in miltipolar mito ses, chromosomal breakage and interchromosomal concatenation events. W e propose that the ability of cells to delay progression into aberrent mitosis, as well as their propensity to undergo apoptosis, are import ant determinants of clinical cytotoxicity. We also suggest that apopto sis plays an important role in preventing the generation of aneuploidy and recombination and rearrangement events commonly associated with c ancer.