MECHANISMS\MICRONUCLEI INDUCTION IN MOUSE MARROW

DUE TO THE SPEED AND SIMPLICITY INVOLVED IN MICRONUCLEI (MN) IDENTIFICATION, MN ANALYSIS HAS BECOME INCREASINGLY USED AS A SENSITIVE, YET LESS EXPENSIVE AND TIME CONSUMING ALTERNATIVE TO CLASSICAL METAPHASE ANALYSIS. THE SCORING OF MN IS ONE OF THE FEW METHODS CURRENTLY AVAILABLE FOR THE DETECTION OF ANEUPLOID-RELATED PROCESSES. ALTHOUGH SEVERAL MN ASSAYS HAVE BEEN DEVELOPED, THE MOST WIDELY USED TEST SYSTEM INVOLVES THE SCORING OF MN IN BONE MARROW OR PERIPHERAL BLOOD POLYCHROMATIC ERYTHROCYTES (PCE) OF MICE. THE FACT THAT MN CAN ALSO ARISE THROUGH A MECHANISM INDEPENDENT OF DNA DAMAGE IS BOTH AN IMPORTANT ATTRIBUTE AND A CONFOUNDING FACTOR. THUS, THE DEVELOPMENT AND APPLICATION OF TECHNIQUES FOR IDENTIFYING THE MECHANISTIC ORIGIN OF MN ARE REQUIRED BEFORE THE INTERPRETATION OF MN DATA CAN EVER BECOME RELIABLE. THE DISCOVERY OF ANTIBODIES AGAINST CHROMOSOME KINETOCHORE REGIONS HAS MADE IT POSSIBLE TO IDENTIFY THE MECHANISTIC ORIGIN OF MN AND THIS METHOD HAS BEEN USED IN VITRO TO IDENTIFY MN WHICH ARISE FROM ABNORMAL CYTOKINESIS. THE PURPOSE OF THIS PROJECT IS TO DEVELOP AND APPLY THIS TECHNIQUE TO MN INDUCED IN MICE BY GENOTOXIC AGENTS.