The frequent exposure to chemicals in the environment and diet leads to the chemical modification of DNA, resulting in the formation of DNA adducts — when a chemical binds to a segment of DNA. Some DNA adducts can induce mutations during cell division, and when occurring in critical regions of the genome, can lead to disease, including cancer.
The National Institute of Environmental Health Sciences (NIEHS) has awarded FIU $164,000 as part of an international collaboration with multiple research institutes and commercial vendors worldwide to develop and curate a comprehensive database of DNA adduct standards.
Anthony De Caprio, associate professor in the department of Chemistry and Biochemistry in the College of Arts, Sciences & Education and Marcus S. Cooke professor in the department of Environmental Health Sciences in the Robert Stempel College of Public Health & Social Work are co-investigators. The team of researchers also includes Jingshu Guo, Peter Villalta, Scott Walmsley and Robert Turesky from the University of Minnesota.
“Basically, DNA adducts can be used as biomarkers of exposure to environmental carcinogens and as biomarkers of adverse effect, in particular cancer, due to such exposure.,” said De Caprio, director of FIU’s Forensic and Analytical Toxicology Facility. “Standardized measurement techniques and MS spectra for the universe of DNA adducts potentially present in human DNA would greatly facilitate the development and use of such biomarkers.”
The targeted analysis of DNA adducts over the past 30 years has revealed that the human genome contains a wide array of DNA adducts, many of which are attributed to life-style factors, such as smoking, eating well-done cooked meats or through oxidative stress. With the advancement of high-resolution mass spectrometry instrumentation and new scanning technologies, untargeted ’omics approaches have become available to simultaneously screen for multiple DNA adducts in a single test. However, the development of this emerging field of DNA adductomics is hindered by the lack of a publicly available mass spectral database for DNA adduct identification and characterization.
“With a database that is freely available and searchable by the public, researchers can quickly identify adduct patterns, which will be very important when using DNA adductomics for assessing human exposures, or identifying cancer causing agents,” said Marcus Cooke environmental health sciences professor in FIU’s Robert Stempel College of Public Health & Social Work. “The successful establishment of a validated DNA adduct mass spectral database in a searchable, reference library is critical for the comprehensive analysis of DNA adductome profiles from cellular DNA, urine, and other biological matrices. This database will facilitate the use of DNA adductomics in human cohort studies and advance our understanding of the relationships between external and internal exposures and disease risk.”
This is Cooke’s fourth, currently active NIEHS grant; having previously received R01, R15, and R41 grants to support his research. DeCaprio has been supported by R01 and R21 grants from NIEHS, NCI, NIOSH, ATSDR, and is currently PI on two grants from NIJ.
Ayleen Barbel Fattal and Jessica Drouet contributed to this article.
