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.
Kaur-S; Pongracz-K; Bodell-WJ; Burlingame-AL
Chem Res Toxicol 1993 Jan; 6(1):125-132
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.
NIOSH-Publication; NIOSH-Grant; Grants-Other; DNA-adducts; Chemical-structure; In-vitro-studies; Molecular-structure; Metabolic-study; Mutagens; Carcinogens
Biomedical & Environ Hlth Scis University of California School of Public Health Berkeley, CA 94720
Chemical Research in Toxicology
University of California Berkeley, Berkeley, California