DNA adducts and you: When bad things happen to good cells

TOXI 121

James Glick, Department of Chemistry & Chemical Biology/Barnett Institute, 360 Huntington Avenue, 102 Hurtig Hall, Boston, MA 02115, Helmut Zarbl, zarbl@eohsi.rutgers.edu, Environmental and Occupational Health Sciences Institute, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, and Paul Vouros, p.vouros@nunet.neu.edu, Department of Chemistry & Chemical Biology/Barnett Institute, Northeastern University, Boston, MA 02115.
DNA damage from chemical exposure represents one potential avenue in the development of cancer. Covalent modification of DNA by foodborne procarcinogen exposure, oxidative stress or from environmental contaminants results in DNA damage that can lead to replication errors and tumor development particularly when the adduct is located on important genes such as the p53 tumor suppressor gene. LC-MS methods, and in particular nanoLC-MS methods, represent important tools for the quantitation of DNA adducts and their relationship to cancer development. Toward that end, we report on the development of sensitive methods for the quantitation of DNA adducts using a Chip-based nanoLC-MS ion trap method and the development of relationships between DNA adduct quantity and DNA microarray screening. Using these two techniques, a genetic fingerprint of DNA damage was developed and compared for DNA adduct formation, mutational spectrum and gene expression profiles for the known foodborne procarcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).