The efficacy of a
leukemia cell transplant model to measure potential chemotherapeutic activity was tested with five different chemicals that had previously been evaluated in 2-year studies. Leukemic spleen cells from Fischer rats were injected subcutaneously into syngeneic recipients and the effects of chemical treatment on
tumor progression were evaluated at 70 days post-transplant. The data from the short-term assay were in all cases correlated with the trends reported for mononuclear cell
leukemia in 2-year studies, where two chemicals were reported to decrease the incidence and three chemicals were reported to increase the incidence of
leukemia. Short-term treatment with the two chemicals which caused negative trends for
leukemia (2-ethoxyethanol or
ethylene glycol monoethyl ether;
4-hexylresorcinol) delayed and/or reduced
tumor growth in the transplant model in a dose-related fashion, as exhibited by reduction or elimination of
splenomegaly and leukoblastosis, and a reversal in the depression of red blood cell indices or platelet counts. By contrast, the rate of
tumor progression was increased in the short-term assay of the three chemicals which previously caused increased trends for
leukemia in 2-year studies (
pyridine; 2,4,6-trichlorophenol,
dichlorvos). The severity of the mononuclear cell
leukemia in the transplant recipients, as measured by histopathological examination of spleen and liver, was correlated with the changes in
tumor growth rates. The in vivo
leukemia transplant model is a short-term assay that could be used to screen a variety of potential chemotherapeutic agents, or to study structure-activity relationships within one class of chemicals.