DEVELOPMENT OF IN VITRO PROPAGATED F344/N MONONUCLEAR CELL LINK

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The high background incidence of mononuclear cell leukemia (MNCL) in Fischer 344 rats (20 to 30%) confounds the evaluation and interpretation of possible chemical treatment related incidence of MNCL in two-year chronic toxicology and carcinogenesis studies. A F344 rat leukemia transplant model has been developed to characterize the biology of this rodent leukemia and to study the tumor biology and determine how chemical treatment effects disease expression. The development and use of in vitro propagated F344/N mononuclear leukemic cells will enhance: (1) development of monoclonal antibodies unique to MNCL for diagnostic purposes and staging of the disease, (2) the use of currently available rate cell surface antigen and receptor data to known cytochemical, morphological and cell biochemistry data and the determination of leukemic cell origin and functional lineage, and (3) the use of in vitro tests to determine the toxicity and carcinogenicity of chemicals under study in the in vivo MNCL transplant model. In vitro propagated mononuclear leukemic cells will be developed from leukemic cells arising in the spleen from in vivo transplanted tumors derived (and periodically rederived) from F344/N rat VM- 12 (isolated at necropsy at the end of a two-year study) that maintain spontaneous MNCL characteristics. Conventional tissue culture techniques based on the known growth and cell culture requirements of hematopoietic and leukemic cells are being used.