TABLE 19

Inhibition of [3H]dUrd incorporation into DNA in L1210 leukemic cells by MTX and Ara-C alone and in (1:0.782) combination L1210 murine leukemic cells (8 × 106 cells) were incubated in Eagle's basal medium in the presence and absence of various concentrations of MTX and Ara-C and their mixture (molar ratio, 1:0.782) at 37°C for 20 min and then incubated with 0.5 μM (1 μCi) of [6-3H]dUrd at 37°C for 30 min. Fractional inhibition (fi or fa) of [6-3H]dUrd incorporation into perchloric acid-insoluble DNA fraction was then measured. All measurements were made in duplicate. Modified from “Quantitative Analysis of Dose-Effect Relationships: The Combined Effects of Multiple Drugs or Enzyme Inhibitors,” Advances in Enzyme Regulation, volume 22, pp 27-55. Copyright 1984 with permission from Elsevier.

MTX Fractional Inhibition (fa) at [Ara-C] of:
0 0.0782 0.156 0.313 0.625 1.25 2.5 5.0
μM
0 0 0.582 0.715 0.860 0.926 0.955 0.980 0.993
0.1 μM 0.0348 0.405
0.2 μM N.D.a 0.587
0.4 μM N.D. 0.775
0.8 μM 0.140 0.878
1.6 μM 0.415 0.943
3.2 μM 0.573 0.970
6.4 μM 0.755 N.D.
  • a Result not used because of large variation between duplicates