A variety of methods have been described to measure cytotoxicity of host effector cells against
tumor targets. While these methods have proven their value, they have certain limitations, most notably that the measured parameter cannot be related to the overall rate of
tumor cell growth. Accordingly, we have developed a new method for measuring cytotoxicity based upon the rates of cell replication and target cell loss. While technically more demanding, this new method has the advantages that the data are biologically relevant to
tumor cell growth and are appropriate for refined statistical analysis of measurements comparing treatment groups. This methodology was applied to macrophage-mediated inhibition of
tumor cell growth.
Proteose peptone-elicited macrophages decreased the rate of
tumor cell loss but also tended to reduce the replicative rate of the
tumor cells so that overall
tumor cell growth was unaffected. In contrast, Bacillus Calmette-Guérin-activated macrophages caused an overall reduction in
tumor cell numbers by increasing the rate of
tumor cell loss (cytolysis) and decreasing the rate of
tumor cell replication (cytostasis). Simultaneously conducted
isotope release assays revealed that the percentage released increased with time but that this did not reflect a change in the rate of cell death. An equation is given relating the rate of survival of control and experimental
tumor cell populations to the commonly used percent specific
isotope release. This relationship explains the dependency of
isotope release on time and provides an explanation why
isotope release did not reliably indicate the relative efficiency of killing by B. Calmette-Guérin-activated macrophages for four different
tumor targets.