Correlating DNA adduct levels and gene expression using LC-MS/MS and DNA microarrays for a foodborne heterocyclic aromatic amine procarcinogen

AEI 4

James Glick, Department of Chemistry & Chemical Biology/Barnett Institute, 360 Huntington Avenue, 102 Hurtig Hall, Boston, MA 02115, Robert Sullivan, Department of Environmental and Occupational Medicine & EOHSI, Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Room 426, Piscataway, NJ 08854, 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@neu.edu, Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Ave, Boston, MA 02115.
Toxicogenomics represents a sophisticated area of research focusing on the integration of data for DNA adduct formation, mutation and gene expression experiments. Among carcinogens in overcooked meat, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is present in high ppb levels. While work has been done to quantitate DNA adduct levels in several systems, the genetic signature for a carcinogen is extremely important. DNA microarrays can be used to provide compound specific gene expression signatures that can be correlated to specific carcinogens, exposure levels, and DNA adduct quantity. Using nanoLC-MS we were able to detect and quantitate DNA adducts in the dosing concentration range of 10-5 to 10-8 M for N-hydroxy-PhIP exposed cells. Gene expression data was used to determine a No Transcriptional Effect Level (NOTEL) following exposure to the active metabolite. The presence of a NOTEL could have significant implications for traditional risk assessment paradigms when extrapolating dose and effect for carcinogens.
 

Academic Employment Initiative
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Academic Employment Initiative

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007