IMMUNOHISTOCHEMICAL ANALYSIS OF BREAST TISSUE DNA DAMAGE

DESCRIPTION (Applicant's Description-edited) Highly specific antisera to carcinogen-DNA adducts have been essential to the development of sensitive immunologic methods for measurement of human exposure to chemical carcinogens. These antisera may also provide important information for understanding the etiology of breast cancer. In this project, the applicant plans to develop quantitative immunoperoxidase methods for the detection of DNA damage in normal and malignant breast tissue applicable to paraffin blocks. Specifically, polycyclic aromatic hydrocarbon (PAH)-DNA adducts and 8- oxodeoxyguanosine (8oxoG) will be measured. When the methods are developed, it will be determined whether they have sufficient sensitivity to detect damage in breast tumor and non-tumor tissue collected from cases in two population-based case-control epidemiologic studies, one in New Jersey and the other on Long Island. In the parent studies, information has been or is being collected on known risk factors including smoking and diet. In the study in New Jersey, paraffin blocks from cases are being analyzed for the presence of overexpressed HER-2/neu and cyclin D and p53 mutation. In the study on Long Island, PAH-DNA will be measured in lymphocytes. Although the studies proposed here are mainly methods development, in a preliminary fashion three specific hypotheses will be tested: increased DNA damage levels in breast tissue result from dietary and lifestyle risk factors (e.g., smoking); mutated or amplified oncogenes or tumor suppressor genes (HER-2/neu, p53 and cyclin D) are found more frequently in women with higher levels of DNA damage; and PAH-DNA adducts in breast tissue correlate with those determined in lymphocytes.