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. 2009 Feb 13;284(7):4090–4101. doi: 10.1074/jbc.M807255200

FIGURE 3.

FIGURE 3.

PNC prevalence reduction by topo I and topo II inhibitors and methotrexate is due to on-target effects. A, 72-h growth inhibition curves were created for camptothecin in the parental DU145 cell line and two clonal DU145 sublines (RC1 and RC0.1), both of which are resistant to camptothecin because of a mutation in the topo I enzyme. The cell lines were treated with camptothecin at the three doses in Table 2 for 72 h, and the PNC prevalence was determined. B, similarly, 72-h growth inhibition curves were created for etoposide in the parental FEMX cell line and two clonal FEMX sublines (FVP1 and FVP3), both of which are resistant to etoposide because of a mutation in the topo II enzyme. The cell lines were treated with etoposide at the three doses in Table 2 for 72 h, and the PNC prevalence was determined. C, 20 μm methotrexate reduces PNC prevalence in HeLa cells, but addition of 100 μm folinic acid in conjunction with methotrexate prevents PNC prevalence reduction. For all experiments error bars =±S.D. (n = 3), and vehicle is 1% DMSO.