CHEMICALLY-INDUCED AND SPONTANEOUS MONONUCLEAR CELL LEUKEMIA IN FISCHER 344 RATS

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NTP chronic toxicity test results indicate a high incidence of rat mononuclear cell leukemia (MNCL) in both control and treated F344 rats. It is difficult to determne if chemical induction of MNCL has occurred in a chronic test because of the high incidence of spontneous MNCL. Responses to chemical treatment have included statistically significant increases or decreses in MNCL as well as positive or negative trends with respect to dose. A transplant model for MNCL has been characterized in terms of its clinical presentation, gross pathology, cell morpholgy and biochemistry, histopathology, and clinical hematology and chemistry. After subcutaneous inoculation of 2 x 10E7 viable leukemic cells into rats, clinical symptoms, morbidity and mortality due to MNCl occur after 100 days (95 to 105 days). Clinical symptoms are usually present after 90 days. However, with this size incoclum, splenomegaly and leukocyte count increase start to occur after 65 days. The FY 1985 objective of this reserch project is to develop a short-term test model for assessing the effect of chemical treatmet on the expression of transplanted mononuclear cell leukemia in F344 male rats.