Schematic representation of an isobologram (Steel and Peckham).

The concentrations that produced 80% cell growth inhibition were expressed as 1.0 on the ordinate and the abscissa of the isobolograms. Envelope of additivity, surrounded by mode I (solid line) and mode II (broken lines) isobologram lines, was constructed from the dose-response curves of STI571 and the combined drug. When the data points of the drug combination fell within the area surrounded by envelope of additivity (Pb), the combination was regarded as additive. When the data points fell to the left of the envelope (Pa), the drug combination was regarded as having a supra-additive effect (synergism). When the points fell to the right of the envelope but within the square or on the square line (Pc), the combination was regarded as having a subadditive effect. When the data points were outside the square (Pd), the combination was regarded as having a protective effect. Both subadditive and protective interactions were regarded as antagonistic effects.