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.