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 perturbations we systematically studied cell cycle perturbations after exposing human ovarian cancer cells to nine commonly used cytotoxic agents. Three principal patterns of cell cycle alterations were observed: a sequential S-G2/M block after exposure to the non-phase-specific agents cis-platinum, 4-hydroperoxy-cyclophosphamide, and mitomycin C (Group I); an isolated G2/M block after exposure to the G2/M phase-specific drugs etoposide and vincristine and the non-phase-specific agent doxorubicin (Group II); and an isolated S block following exposure to the S phase-specific agents 5-fluorouracil, methotrexate, and cytosine arabinoside (Group III). Overall, there was no direct correlation between the degree of cell cycle perturbations and chemosensitivity. However, when the three subgroups of non-phase-specific agents, S phase-specific agents, and G2/M-specific agents were analyzed separately, positive correlations between the magnitude of cell kinetic alterations and chemosensitivity were observed. Cell kinetic alterations appeared to precede cytotoxicity.
Petru
E
E
Department of Obstetrics and Gynecology, School of Medicine, University of Graz, Austria.
Sevin
B U
BU
Haas
J
J
Ramos
R
R
Perras
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents