4-Aminobiphenyl (4-ABP) - DNA Damage in Breast Tissue and Relationship to p53 Mutations and Polymorphisms of Metabolizing Genes

The proposed research project investigates the relationship between exposure to cigarette smoke and genetic susceptibility factors. Levels of 4-aminobiphenyl 4-ABP-DNA adducts in breast tumor tissue sections were the same between smokers and non-smokers. The project will also investigate whether an association exists between 4-ABP-DNA adducts and the carcinogen metabolizing genes CYP1A2 and NAT2. The analysis of the CYP1A2 gene is currently in progress. Due to the difficulty in obtaining large fragments of DNA from the tumor tissue sections required for PCR-RFLP, a new method is under development for genotyping NAT2. Another aim of this project is to determine if environmental chemicals and their metabolites can cause mutations in the p53 gene. We hope to analyze the mutations in p53 with the innovative Affymetrix system recently purchased by Columbia University. After the completion of advanced course work in statistics and epidemiology this fall, the correlations made between adduct levels and genotyping data of the metabolizing enzymes will be available for next years report.