Development and validation of a cellular transplant model for leukemia in Fischer rats: a short-term assay for potential anti-leukemic chemicals.
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.
Dieter
M P
MP
National Institutes of Health, National Toxicology Program, Research Triangle Park, NC 27709.
Jameson
C W
CW
French
J E
JE
Gangjee
S
S
Stefanski
S A
SA
Chhabra
R S
RS
Chan
P C
PC
D000818:Animals; D000970:Antineoplastic Agents; D001681:Biological Assay; D002273:Carcinogens; D002733:Chlorophenols; D004006:Dichlorvos; D005026:Ethylene Glycols; D007942:Leukemia, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D011725:Pyridines; D051381:Rats; D011916:Rats, Inbred F344; D012118:Resorcinols; D013154:Spleen / Q000033:anatomy & histology
D000970:Antineoplastic Agents; D002273:Carcinogens; D002733:Chlorophenols; D005026:Ethylene Glycols; D011725:Pyridines; D012118:Resorcinols; D004006:Dichlorvos; C021296:2-ethoxyethanol; C024564:2,4,6-trichlorophenol; C023666:pyridine