A CORRELATION OF CELL-CYCLE PERTURBATIONS WITH CHEMOSENSITIVITY IN HUMAN OVARIAN-CANCER CELLS EXPOSED TO CYTOTOXIC DRUGS IN-VITRO

To test the association between cytotoxicity and in vitro cell cycle p erturbations we systematically studied cell cycle perturbations after exposing human ovarian cancer cells to nine commonly used cytotoxic ag ents. Three principal patterns of cell cycle alterations were observed : a sequential S-G2/M block after exposure to the non-phase-specific a gents cis-platinum, 4-hydroperoxy-cyclophosphamide, and mitomycin C (G roup I); an isolated G2/M block after exposure to the G2/M phase-speci fic drugs etoposide and vincristine and the non-phase-specific agent d oxorubicin (Group II); and an isolated S block following exposure to t he S phase-specific agents 5-fluorouracil, methotrexate, and cytosine arabinoside (Group III), Overall, there was no direct correlation betw een the degree of cell cycle perturbations and chemosensitivity, Howev er, when the three subgroups of non-phase-specific agents, S phase-spe cific agents, and G2/M-specific agents were analyzed separately, posit ive correlations between the magnitude of cell kinetic alterations and chemosensitivity were observed, Cell kinetic alterations appeared to precede cytotoxicity. (C) 1995 Academic Press, Inc.