Monoclonal Antibodies to DNA Base Lesions

Characteristic base lesion profiles from hydroxyl-radical induced oxidative damage occur in DNA frobreast tissue compared to DNA from invasive ductal carcinomas or histologically normal breast tissuepatients. These profiles shift from predominantly non-mutagenic lesions in non-cancer tissues to muttissues, regulated, most probably, the cellular redox potential. Evidence indicates the nature of DNpredictive of future breast cancer risk. These lesions are quantifiable using gas-chromatography-masHPLC analyses on isolated and derivatized DNAs. The objective is to develop DNA base lesion-specificantibodies to establish a quantitative immunoassay. Such an assay would provide a reliable quantitacost technology with critical importance in future clinical applications. Base lesion haptens will bcarrier protein for immunization in mice. Hybridomas will be screened for lesion specificity, bindiantigen binding response. Initial characterization of antibodies will involve analysis of hapten cophysiological DNA specimens of known base lesion concentration as determined by standard gas-chromatspectrometric determinations. Based upon these results, antibodies will be selected for their suitadevelopment of immunoassays.