IS THERE A CORRELATION BETWEEN CELL-CYCLE PERTURBATIONS AND CHEMOSENSITIVITY IN OVARIAN-CANCER CELLS EXPOSED TO CYTOTOXIC DRUGS IN-VITRO

Objectives: Is there a correlation between cell cycle perturbations an d cytotoxicity in ovarian cancer cells exposed to cytotoxic drugs in v itro? Methods: We tested the association between cytotoxicity and in v itro cell cycle perturbations after exposure of human ovarian cancer c ells to seven cytotoxic agents. Results: Three principal patterns of c ell cycle alterations were observed: a sequential S-G/M block after ex posure to the non phase-specific agents cis-platinum, 4-hydroperoxy-ey clophosphamide, and mitomycin C (Group I); an isolated G2/M block afte r exposure to the G2/M phase-specific drugs etoposide and vincristine (Group II); and an isolated S block following exposure to the S phase- specific agents 5-fluorouracil and cytosine arabinoside (Group III). O verall, there was no direct correlation between the degree of cell cyc le perturbations and cytotoxicity. However, when the three subgroups o f phase non-specific agents, S phase-specific agents, and G2/M specifi c agents were analyzed separately, positive correlations between the m agnitude of cell kinetic alterations and cytotoxicity were observed. C onclusions: Cell kinetic alterations appeared to precede cytotoxicity. This experimental model may be particularly useful to study cell kine tic effects after high-dose chemotherapy since, in contrast to convent ional chemotherapy, the magnitude of cell kinetic perturbations after this kind of treatment is significantly increased.