Mechanism of resistance of non-cycling mammalian cells to 4'-[9-acridinylamino]methanesulphon-m-anisidide: role of DNA topoisomerase II in log- and plateau-phase CHO cells.
CHO-AA8 cells were used as a model system to study the role of DNA topoisomerase II in the resistance of non-cycling cells to amsacrine. Plateau-phase AA8 cells have previously been shown to be resistant to amsacrine and to contain fewer DNA breaks than log-phase cells after drug treatment (Robbie, M.A., Baguley, B.C., Denny, W.A., Gavin, J.R. and Wilson, W.R. (1988) Cancer Res., in press). The phage P4-unknotting activity of nuclear extracts decreased 2-fold when AA8 cells entered into the non-cycling state, but there was no difference in sensitivity to amsacrine between log- and plateau-phase nuclear extracts. Drug stimulation of protein-DNA complex formation was similar in whole cells, isolated nuclei and nuclear extracts from either log- or plateau-phase cells. However, stimulation of complex formation in cells, nuclei or nuclear extracts was approx. 4-fold lower in plateau-phase than in log-phase. The data presented suggested that drug-enzyme interaction was altered in plateau-phase cells.
Schneider
E
E
Department of Cellular and Molecular Biology, University of Auckland, New Zealand.
Darkin
S J
SJ
Robbie
M A
MA
Wilson
W R
WR
Ralph
R K
RK
D000677:Amsacrine / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004250:DNA Topoisomerases, Type II / Q000502:physiology*; D004351:Drug Resistance; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D059005:Topoisomerase II Inhibitors
D009687:Nuclear Proteins; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D004250:DNA Topoisomerases, Type II