TO REDUCE THE UNCERTAINTY IN ESTIMATES OF CANCER AND CARDIOVASCULAR RISKS FROM SPACE RADIATION WE WILL EVALUATE CHANGES IN MOLECULAR BIOMARKERS IN RODENTS AND RABBITS EXPOSED TO IONS RELEVANT TO EXPOSURES OF ASTRONAUTS IN THE SPACE ENVIRONMENT. SERUM HEART LIVER AND LUNG TISSUES COLLECTED FROM EXPOSED ANIMALS AND MATCHING CONTROLS WILL BE USED FOR BIOMARKER DISCOVERY FOLLOWING SYSTEMSBIOLOGY APPROACHES. THE STUDY WILL USE MODERN ANALYTIC TECHNOLOGIES AND RIGOROUS STATISTICS FOR ASSESSING CHANGES IN EXPRESSION OF MICRORNAS (MIRNAS) LONG NON-CODING RNAS (LNCRNAS) AND MESSENGER RNAS (MRNAS) ASSOCIATED WITH CLINICAL ENDPOINTS FOR MECHANISTIC UNDERSTANDING OF DISEASE INITIATION AND PROGRESSION. ANALYSIS OF SAMPLES FROM PATIENTS RECEIVING RADIATION THERAPY AND ORGAN TARGETED AND ORGAN PROTECTED LOW-LET IRRADIATION MODEL STUDIES HAVE SHOWN CHANGES IN CIRCULATING MIRNAS ORIGINATING FROM ORGAN SYSTEMS AS A FUNCTION OF DOSE AND TIME CORRELATING WITH DISEASE STATES. ARCHIVED CARDIAC SPECIMENS FROM RABBITS AND RATS PREVIOUSLY EXPOSED TO 0.5 GY PROTON OR OXYGEN IONS WITH RESPECTIVE SHAM CONTROLS WILL BE USED FOR DISCOVERY AND VALIDATION OF SPACE RADIATION-INDUCED CARDIOVASCULAR DISEASES. CHANGES IN MIRNAS MECHANISTICALLY CONNECTED TO INFLAMMATION AND PATHOLOGICAL CHANGES USING CLINICAL IMAGING AND BIOCHEMICAL ENDPOINTS OF CARDIOVASCULAR DISEASES WILL BE EVALUATED. MIRNAS AND LNCRNAS IN LUNG LIVER AND SERUM COLLECTED FROM MICE EXPOSED TO 0.2 GY SILICON IONS WILL BE COMPARED WITH SHAM CONTROLS OF CHANGES IN CANCER ENDPOINTS. THE AVAILABILITY OF SPECIMENS (ARCHIVED OR UPCOMING SACRIFICES) FROM ON-GOING OR COMPLETED CARCINOGENESIS NSCOR AND NSBRI CENTER FOR SPACE RADIATION RESEARCH STUDIES FOCUSING ON CARDIOVASCULAR DISEASES ARE ENSURED. OUR PROJECT IS COST-EFFECTIVE AND UNIQUE BECAUSE WE WILL USE SAMPLES BOTH FOR DEVELOPING CANCER AND CARDIOVASCULAR RISK ASSESSMENT. CELLULAR AND MOLECULAR MECHANISMS INVOLVED IN SPACE RADIATION-INDUCED CARDIOVASCULAR DISEASE LUNG AND LIVER CANCER WILL BE STUDIED WHICH WILL SIGNIFICANTLY CONTRIBUTE TO THE TESTING OF AND VALIDATING EFFECTIVE COUNTERMEASURES.