Cell cycle effects of the novel topoisomerase I inhibitor NU/ICRF 505 in a panel of Chinese hamster ovary cell lines.
The effect of the novel topoisomerase I inhibitor NU/ICRF 505 (20 microM, approximate IC50 concentration) on the cell cycle was studied by flow cytometry in four Chinese hamster ovary (CHO) cell lines. Postdrug treated cells were incubated with optimal concentrations of cytochalasin B to prevent re-entry of daughter cells into the cell cycle. NU/ICRF 505 had no significant effect on cell cycle distribution in the parent cell line (CHO-K1) and two mutants hypersensitive to topo II inhibitors (ADR-1, ADR-3), all of which express similar levels of topo I protein. In the drug-resistant variant ADR-r, which overexpresses topo I 2-fold, a significant accumulation of cells in G1 phase was recorded. These results are broadly consistent with the cell cycle effects expected in CHO cells by a classic topo I poison (camptothecin) and add weight to the view that NU/ICRF 505 induces cell death primarily through topo I inhibition.
Macpherson
J S
JS
Imperial Cancer Research Fund, Medical Oncology Unit, Western General Hospital, Edinburgh, U.K.
Cummings
J
J
Meikle
I
I
Miller
E P
EP
Smyth
J F
JF
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D006224:Cricetinae; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004351:Drug Resistance; D005434:Flow Cytometry; D059004:Topoisomerase I Inhibitors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000880:Anthraquinones; C100645:NU-ICRF 505; D059004:Topoisomerase I Inhibitors; D014443:Tyrosine; D004264:DNA Topoisomerases, Type I