IN VITRO MODELS FOR HEMOTOXICITY AND HEPATOTOXICITY

THE RESEARCH WILL DEVELOP IN VITRO MODELS FOR HEMOTOTOXICITY AND HEPATOTOXICITY. PARENCHYMAL CELL GROWTH IS ACHIEVED ON AN NSC WITH STROMAL SUPPORT CELLS FROM THE ORGAN UNDER STUDY. THE BM NSC HAS A MULTILINEAGE HEMATOLOGIC CHARACTER PERSISTING FOR MONTHS. THE L NSC EXHIBITS ALBUMIN SYNTHESIS, DRUG METABOLIZING CAPACITY, AND PROLIFERATION. THE EFFECTS OF CHEMOTHERAPEUTIC AND INDUSTRIAL AGENTS ON BN AND/OR L NSC WILL BE DETERMINED. BM NSC WILL BE ANALYZED BY FLOW CYTOMETER FOR PHENOTYPIC CHARACTERISTICS, CELL CYCLE STATUS, AND BY ASSESSING THE ABILITY OF CELLS DERIVED FROM THE CULTURES TO FORM HEMATOPOIETIC IN AGAR GELS. L NSC WILL BE ANALYZED FOR ALBUMIN PRODUCTION, ENZYME RELEASE, DRUG METABOLIZING CAPACITY, AND PROLIFERATION OF PARENCHYMA. BM NSC WILL BE EXPOSED TO DRUGS THAT REQUIRE BIOACTIVATION WHILE IN THE PRESENCE OF L NSC. PRELIMILARY RESULTS INDICATE DIFFERENTIAL EFFECTS ON HEMATOPOIESIS IN BN NSC IN THE PRESENCE OF L NSC WHEN BM NSC WERE EXPOSED TO AGENTS SUCH AS CYCLOPHOSPHOMIDE OR BENZENE. BM AND/OR L NSC MAY BE DEVELOPED INTO SCREENING TESTS FOR SCREENING COMPOUNDS PRIOR TO COMMITMENT TO WHOLE ANIMAL TESTING.