TY - JOUR
T1 - Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3) human ovarian cancer cells
T2 - Correlations with the formation of DNA double-strand breaks
AU - Noviello, Elvira
AU - Aluigi, MariaGrazia
AU - Cimoli, Guido
AU - Rovini, Elisabetta
AU - Mazzoni, Alessandra
AU - Parodi, Silvio
AU - De Sessa, Fabio
AU - Russo, Patrizia
PY - 1994/11/1
Y1 - 1994/11/1
N2 - Dexorubicin, 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.
AB - Dexorubicin, 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.
KW - Aberrations
KW - Atypical multi-drug resistance
KW - Ovarian cancer
KW - Sister-chromatid exchange
KW - Topoisomerase II
UR - http://www.scopus.com/inward/record.url?scp=0028004483&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028004483&partnerID=8YFLogxK
U2 - 10.1016/0027-5107(94)90069-8
DO - 10.1016/0027-5107(94)90069-8
M3 - Article
C2 - 7526171
AN - SCOPUS:0028004483
SN - 0027-5107
VL - 311
SP - 21
EP - 29
JO - Mutation Research
JF - Mutation Research
IS - 1
ER -