The long-term objectives of this project are to establish a stable source of well-characterized antibodies to DNA adducts of carcinogen/mutagens, so that these important probes can be made available for fundamental research into the mechanism(s) of carcinogenesis, and to provide services/assay kits for monitoring human populations for possible exposure to some environmental carcinogens by screening for """"""""neo-antigens"""""""" in biological specimens.
Specific aims for the Phase I effort will include the production of acrolein:DNA adducts by treating calf thymus DNA in vitro with varying concentrations of the chemical, so as to obtain DNA samples containing different levels of reaction, and utilization of a number of innovative immunological methods that would reduce the amount of immunogen and/or to increase the efficiency of antibody production (use of RBF/DN mice with a marker chromosome that contain the genes for both APRT and immunoglobin heavy chain, use of HL-653 cells deficient in both HPRT and APRT as the fusion partner, in vitro immunizaitaon with or without protein coupling, intrasplenic immunization, use of alternate adjuant system).
