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OUR PRIMARY GOAL IS TO TEST THE EFFICACY OF APIGENIN (AP) FOR PREVENTION AND MITIGATION OF CANCER DUE TO SPACE RADIATION EXPOSURE AS MEASURED BY INCIDENCE AGGRESSIVENESS BURDEN AND LATENCY. OUR MAIN HYPOTHESIS IS THAT AP EXHIBITS ITS BENEFICIAL EFFECTS BY SUPPRESSION OF RADIATION-INDUCED INFLAMMATION AND OXIDATIVE STRESS DURING THE INITIATION/PROMOTION STEPS OF CARCINOGENESIS. ALTHOUGH THE EMPHASIS WILL BE THE MITIGATION OF LUNG CANCER AND LYMPHOMA/LEUKEMIA OTHER TYPES OF CANCER WILL BE RECORDED. APIGENIN (AP) IS A DIETARY SUPPLEMENT KNOWN TO POSSESS POTENT ANTIOXIDANT ANTI-INFLAMMATORY AND ANTI-CANCER ACTIVITIES IN VARIOUS TISSUES. WE ARE THE FIRST TO REPORT THAT AP PROTECTS HUMAN LYMPHOCYTES FROM EXPOSURE TO RADIATION IN VITRO AND THAT AP ATTENUATES INFLAMMATION AND OXIDATIVE DAMAGE IN BONE MARROW CELLS OF MICE EXPOSED TO RADIATION. THESE FINDINGS LAY THE GROUNDWORK FOR THIS PROJECT. WE WILL GIVE FOOD CONTAINING AP TO MICE (MALES AND FEMALES) BEFORE AND AFTER EXPOSURE TO SILICON (SI) IONS. SUBSEQUENTLY THE MIXED BEAM (PROTONS + SI) EXPERIMENT WILL BE DESIGNED. OXIDATIVE STRESS AND INFLAMMATION ARE HIGHLY RELEVANT NOT ONLY TO CARCINOGENESIS BUT ALSO TO CARDIOVASCULAR AND NERVOUS DISORDERS. HENCE GROUPS OF MICE FROM EACH TREATMENT WILL BE USED FOR A SERIAL SACRIFICE SCHEDULE AT 1 WEEK AND 3 MONTHS POST-IRRADIATION. THIS WILL TEST THE ABILITY OF AP TO COUNTERACT HEAVY-ION-INDUCED EARLY- AND LATE-OCCURRING INFLAMMATION AND OXIDATIVE DAMAGE IN VARIOUS TISSUES LINKED TO CANCER THAT ARE THE FOCUS OF OUR STUDY (I.E. BONE MARROW LUNG THYMUS SPLEEN) INCLUDING THE HEART AND THE BRAIN OF THE SAME MOUSE. ALL REMAINING MICE WILL BE OBSERVED FOR MORBIDITY AND MORTALITY UNTIL THEY REACH ABOUT 800 DAYS OF AGE. OUR DATA ENABLE THE EVALUATION OF COUNTERMEASURE EFFICACY OF AP NOT ONLY ACROSS TISSUES AT RISK FOR CANCER BUT ALSO ACROSS RISK AREAS. THIS MULTI-TISSUE APPROACH HAS NOT BEEN USED IN SPACE RESEARCH.

$946,184FY2020National Aeronautics and Space AdministrationNASA

The Research Foundation For The State University Of New York

Investigators

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