Bis(hydroxyphenylethyl)deoxyguanosine adducts identified by phosphorus-32-postlabeling and four-sector tandem mass spectrometry: unanticipated adducts formed upon treatment of DNA with styrene 7,8-oxide

Details

• Personal Author:
  Bodell WJ ; Burlingame AL ; Kaur S ; Pongracz K
• Description:
  The phosphorus-32 (P-32) postlabeling procedure was in order to detect covalent xenobiotic adducts in the enzymic hydrolysate of native calf thymus DNA modified during incubation with styrene-oxide (96093). Six covalent adducts were detected by this method, three of which were very hydrophobic, indicating they may have been unusually modified. These three were studied and their structural nature presented as isomeric bis substituted guanine mononucleotides. These three represented less than 2% of the total adducts detected. Elemental composition was determined by measuring their accurate masses by high resolution mass spectrometry. This demonstrated the incorporation of 2 moles of hydroxyphenylethyl moieties. Interpretation of high energy collision induced dissociation mass spectra, along with ultraviolet/visible and fluorescence spectrophotometry allowed the identification of N2-(2- hydroxy-1-phenylethyl)-O6-(2-hydroxy-2-phenylethyl)-2'- deoxyguanosine 3'-phosphate, N2-(2-hydroxy-1-phenylethyl)-O6-(2- hydroxy-1-phenylethyl)-2'-deoxyguanosine 3'-phosphate, and N1,N2- bis(2-hydroxy-1-phenylethyl)-2'-deoxyguanosine-3'-phosphate. The other most abundant adducts represented about 65% of the total covalent binding and were identified as depurinated N7-substituted guanines using tandem mass spectrometry with ultraviolet/visible spectroscopy. The authors recommend the use of combined advanced techniques for a comprehensive strategy which insures complete structural identification of all xenobiotic/DNA adducts. [Description provided by NIOSH]
• Subjects:
  Carcinogens Chemistry Energy Metabolism Mutagens Occupational Health Safety
• Keywords:
  Chemical-structure DNA-adducts Grants-Other In-vitro-studies Metabolic-study Molecular-structure NIOSH-Grant NIOSH-Publication
• ISSN:
  0893-228X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  125-132
• Volume:
  6
• Issue:
  1
• NIOSHTIC Number:
  nn:00212969
• Citation:
  Chem Res Toxicol 1993 Jan; 6(1):125-132
• Contact Point Address:
  Biomedical & Environ Hlth Scis University of California School of Public Health Berkeley, CA 94720
• CAS Registry Number:
  Styrene oxide (CAS RN 96-09-3)
• Federal Fiscal Year:
  1993
• Performing Organization:
  University of California Berkeley, Berkeley, California
• Peer Reviewed:
  True
• Start Date:
  19850901
• Source Full Name:
  Chemical Research in Toxicology
• End Date:
  19931227
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fc8ff34a5d1bd6a59ea711717bd1833df2da64884ed6547b95f639d93dba5dff351a538608e1d2562e2741d74f1e74978e192e38a96b222366fa9ba519d49456
• Download URL:
  https://stacks.cdc.gov/view/cdc/204254/cdc_204254_DS1.pdf
• File Type:
  [PDF - 3.54 MB ]