The measurement of DNA adducts provides important information about human exposure to genotoxic chemicals and can be employed to elucidate mechanisms of DNA damage and repair. DNA adducts can serve as biomarkers for interspecies comparisons of the biologically effective dose of procarcinogens and permit extrapolation of genotoxicity data from animal studies for human risk assessment. One major challenge in DNA adduct biomarker research is the paucity of fresh frozen biopsy samples available for study. However, archived formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis of disease are often available. We have established robust methods to recover DNA free of crosslinks from FFPE tissues under mild conditions which permit quantitative measurements of DNA adducts by liquid chromatography-mass spectrometry. The technology is versatile and can be employed to screen for DNA adducts formed with a wide range of environmental and dietary carcinogens, some of which were retrieved from section-cuts of FFPE blocks stored at ambient temperature for up to nine years. The ability to retrospectively analyze FFPE tissues for DNA adducts for which there is clinical diagnosis of disease opens a previously untapped source of biospecimens for molecular epidemiology studies that seek to assess the causal role of environmental chemicals in cancer etiology.
Bibliographical noteFunding Information:
The work cited in this review conducted by the Turesky laboratory has been supported by Grants R01ES019564 and R21ES014438 from the National Institute of Environmental Health Sciences, R01CA122320, R01CA220367, and R33CA186795, and the National Center for Advancing Translational Sciences award number UL1TR000114 from the National Cancer Institute of the National Institutes of Health. Mass spectrometry was carried out in Analytical Biochemistry Shared Resources of the Masonic Cancer Center, University of Minnesota, funded in part by Cancer Center Support Grant CA-077598
- DNA adducts
- Formalin-fixed paraffin-embedded tissues
- Mass spectrometry