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Professor
Roger W. Giese's Research Group
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..

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.

Dr. Poguang Wang
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