THE FORMATION OF DNA-CARCINOGEN ADDUCTS IS AN IMPORTANT ENVIRONMENTAL FACTOR IN CARCINOGENESIS.

THE FORMATION OF DNA-CARCINOGEN ADDUCTS IS AN IMPORTANT ENVIRONMENTAL FACTOR IN CARCINOGENESIS. RECENT TECHNIQUES FOR ISOLATION AND CHARACTERIZATION OF DEOXYNUCLEOSIDE-CARCINOGEN ADDUCTS AND SUBSEQUENT IMMUNOASSAY PROCEDURES CAN EFFECTIVELY DETECT THESE ADDUCTS FROM CELL LYSATES IN THE RANGE OF 1 ADDUCT/107 BASES. WE WILL USE OUR COMBINED TECHNICAL EXPERTISE IN THE AREAS OF NUCLEOTIDE/NUCLEOSIDE CHEMISTRY AND CHROMATOGRAPHY, AND IMMUNOLOGY IN A PHASE I STUDY FOR PRODUCTION OF MONOCLONAL ANTIBODIES TO ACROLEIN AND 1-NITROPYRENE ADDUCTS TO DEOXYNUCLEOSIDES AS THE MODEL SYSTEMS. AFTER DEMONSTRATION OF FEASIBILITY OF THE TECHNOLOGY AND COMPLETION OF THE PHASE I OBJECTIVES, PHASE II STUDIES WILL USE THE EXPERIMENTAL PROTOCOLS AND PHASE I EXPERIENCE TO INVESTIGATE ADDITIONAL CARCINOGENS AND MINOR ADDUCTS LISTED IN THE REQUEST. ADDUCTS FORMED WITH RIBONUCLEOSIDES WHICH MAY HAVE HIGHER TURNOVER RATES WILL ALSO BE STUDIED IN PHASE II. THE LONG-TERM OBJECTIVE OF THE PROJECT IS TO DEVELOP NONINVASIVE, ACCURATE, ECONOMICAL, SENSITIVE, AND SELECTIVE IMMUNOASSAY TEST KITS FOR MONITORING PERSONNEL EXPOSURE TO CARCINOGENS.