THE LONG-TERM OBJECTIVE OF THIS PROJECT IS TO ESTABLISH A STABLE SOURCE OF WELL-CHARACTERIZED ANTIBODIES TO DNA ADDUCTS OF CARCINOGENS/MUTAGENS, SO THAT THESE IMPORTANT PROBES CAN BE MADE AVAILABLE FOR RESEARCH INTO MECHANISM(S) OF CARCINOGENESIS, AND

THE LONG-TERM OBJECTIVE OF THIS PROJECT IS TO ESTABLISH A STABLE SOURCE OF WELL-CHARACTERIZED ANTIBODIES TO DNA ADDUCTS OF CARCINOGENS/MUTAGENS, SO THAT THESE IMPORTANT PROBES CAN BE MADE AVAILABLE FOR RESEARCH INTO MECHANISM(S) OF CARCINOGENESIS, AND FOR MOLECULAR CANCER EPIDEMIOLOGY TO MONITOR HUMAN POPULATIONS FOR POSSIBLE EXPOSURE TO ENVIRONMENTAL CARCINOGENS. PHASE I EFFORTS INVOLVE: A.PRODUCTION OF DNA ADDUCTED WITH DIFFERENT LEVELS OF THE ANTI ISOMER, 1,2-DIOL-3,4-EPOXIDE, ONE OF THE ULTIMATE CARCINOGENIC METABOLITES OF THE ENVIRONMENTAL CARCINOGEN, 5-METHYLCHRYSENE (ACHIEVED BY TREATING CALF THYMUS DNA UNDER DIFFERENT CONDITIONS IN VITRO) TO BE USED AS A HAPTEN FOR THE IMMUNOGEN AND AS THE SOLID PHASE IN ENZYME-LINKED IMMUNOSORBENT ASSAYS. B.UTILIZATION OF DIFFERENT IMMUNIZATION METHODS (IN VITRO AND INTRASPLENIC, IN ADDITION TO CONVENTIONAL IN VIVO METHODS) SO THAT THE AMOUNT OF IMMUNOGEN NEEDED COULD BE REDUCED, HENCE HELPING IN THE PRODUCTION OF A VARIETY OF MONOCLONAL AND/OR ""DEFINED'' POLYCLONAL ANTIBODIES. DURING PHASE I, RABBIT ANTISERA WILL BE RAISED AGAINST THE DNA ADDUCTED WITH 5-METHYLCHRYSENE, IN ADDITION TO MONOCLONALS THAT CAN DETECT SOME OF THESE LESIONS IN DNA. SUCCESS IN THESE ENDEAVORS WILL ENSURE THE FEASIBILITY OF THE OVERALL PROGRAM AND PAVE THE WAY FOR DEVELOPMENTAL STUDIES OF PHASE II, AS WELL AS TO THE EVENTUAL PRODUCTION OF ASSAY KITS FOR DETERMINING SUCH