The Barnett Institute

Research

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  Karger
  Hancock
  Jones
  Vouros
  Giese
  Giessen
  Engen
  Zhou

Research Group of Prof. Roger W. Giese

Recent advances have been made in four areas, all concerning the measurement of carcinogen-modified nucleotides, termed DNA adducts. First, using a mass tag prepared recently in our laboratory, which boosts nucleotide response by MALDI-TOF-MS, we arediscovering the exact masses of unknown DNA adducts in autopsy human lung tissue. Second, an electron capture mass spectrometer (EC-MS) assay was developed and used to measure an ethylene oxide DNA adduct in small blood samples from hospital workers potentially exposed to this carcinogenic sterilization gas. Significantly, the adduct was detected over a 150-fold range, 30 times greater than a prior literature report based on a less definitive method; a broad detectable range for DNA adducts enhances their usefulness as biomarkers. Third, also based on EC-MS, we have established an assay for glycolate which is 100-fold more sensitive than prior procedures. Fourth, we have established a practical method for large-scale extraction of DNA from mammalian tissues and conversion to DNA nucleotides, free of ribonucleotides. Overall, this work, which is part of the Environmental Cancer Research Program, is targeted to improve the usefulness of DNA adducts as biomarkers for cancer or cancer risk..

mass spectrum of 10 compounds

Fig 1: Simultaneous detection of 50 fmol each of four mass tag-labeled normal deoxynucleotides, five DNA adducts (N2-ethyl-G, 1,N6-etheno-A, 8-oxo-G, benzo[a]pyrene-A and benzo[a]pyrene-G), and an internal standard (N2-ethyl-d4-G) by MALDI-TOF-MS.

photo of poguang wang
Dr. Poguang Wang

Last Updated 3/30/09