DEVELOPMENT OF IN VITRO PROPAGATED F344/N MONONUCLEAR CELL LINES

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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 rat 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. To date several hybridoma cell lines have been developed that have been determined to secrete antibodies that may be unique to these leukemic cells. Cell separations have been developed that allow separation of different leukemia cell types. These different subsets of leukemia cells have been propagated in vivo through several passages and have been cryopreserved for future characterization, (including monoclonal antibody analysis). and in vitro culture as the methods for diffusion chamber, soft agar, and Dexter type cultures and culture conditions are refined.