The goal of this project is to characterize the role of nutritional and endocrine factors in the progression of mononuclear cell leukemia (MNCL) in Fischer 344/N (F344) rats, with emphasis placed on explaining documented idiosyncrasies in the occurrence of this tumor. We will achieve our goal by first testing the hypothesis that nutritional manipulations and experi- mental-induced alterations in selected hormones/growth factors influence the incidence and latency period of MNCL in F344 rats using a short-term in vivo transplant model. These whole animal treatments will be further characterized for their ability to alter cellular proliferation and differentiation of MNCL cells using a diffusion chamber system in situ. Our experiments have been designed to explain idiosyncrasies in spontaneous MNCL incidence, Including gender differences in background incidence and in response to corn oil gavage. Successful completion of our goal will provide guidance for reducing variability and decreasing the spontaneous incidence of MNCL in F344 rats. This will lead to increased statistical power, reduced confounding and clarified interpretation of carcinogen bioassay data used in risk assessment. Our long-term objective is to establish well-defined laboratory models for evaluating chemical, nutritional and endocrine modulations on leukemia progression. This work represents a collaborative effort between nutri- tional scientists at the University of North Carolina and toxicologists at the National Institute of Environmental Health Sciences.
