Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3) human ovarian cancer cells: correlations with the formation of DNA double-strand breaks.
Doxorubicin, ellipticine and etoposide are antineoplastic drugs with topoisomerase II inhibitory activity. The relationship between drug-induced sister-chromatid exchanges (SCEs) or chromosomal aberrations (CAs) and cytotoxicity, or drug-induced DNA double-strand breaks (DSBs) and cytotoxicity, or drug-induced SCEs and DSBs was investigated in human ovarian cancer cells sensitive (A2780) and resistant (A2780-DX3) to topoisomerase II inhibitors. 30-min drug treatments produced SCEs, CAs and DSBs in sensitive cells, doxorubicin being more potent than etoposide at equimolar concentrations. The same treatments of resistant (A2780-DX3) cells did not produce chromosomal damage (SCEs, CAs, DSBs) and no cytotoxicity was observed. A plot of cytotoxicity versus SCEs indicated a good correlation between these two parameters for topoisomerase II inhibitors and not for mytomicin C. The plot of DSBs versus SCEs also showed a very good correlation.
Noviello
E
E
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Aluigi
M G
MG
Cimoli
G
G
Rovini
E
E
Mazzoni
A
A
Parodi
S
S
De Sessa
F
F
Russo
P
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D010051:Ovarian Neoplasms; D012854:Sister Chromatid Exchange; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D059005:Topoisomerase II Inhibitors; D016685:Mitomycin; D005047:Etoposide; D004317:Doxorubicin