Characterization of an adduct and its degradation product produced by the reaction of cyanoethylene oxide with deoxythymidine and DNA.
Cyanoethylene oxide (CEO), the putative toxic and carcinogenic metabolite of acrylonitrile, is a direct-acting mutagen. CEO reacted with deoxythymidine (dT) to form a single adduct (approximately 3% dT modified). Using two-dimensional NMR spectroscopy and fast atom bombardment mass spectrometry, this adduct was identified as N3-(2-cyano-2-hydroxyethyl)deoxythymidine. Subsequently, degradation of the adduct yielded N3-(2,2-dihydroxyethyl)deoxythymidine, a hydrated form of N3-(oxoethyl)deoxythymidine. N3-(2-cyano-2-hydroxyethyl)deoxythymidine was also detected in the reaction of [2,3-14C]CEO with calf thymus DNA. Small UV peaks, not present in the control, were detected from the reaction of CEO with dA, dG and dC. However, neither their retention times nor spectral characteristics corresponded with the standards used in this study. Characterization of this cyano-hydroxyethyl adduct and its degradation product following in vitro exposure of nucleosides to CEO may provide insight as to the types of adducts that could be assessed as biomarkers in vivo, and the modifications responsible for the mutational effects of CEO.
Yates
J M
JM
Department of Chemistry, North Carolina State University, Raleigh 27695.
Summer
S C
SC
Turner
M J
MJ
Recio
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L
Fennell
T R
TR
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D005027:Ethylene Oxide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens / Q000633:toxicity*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013936:Thymidine / Q000737:chemistry*
D009153:Mutagens; C033154:2-cyanoethylene oxide; D004247:DNA; D005027:Ethylene Oxide; D013936:Thymidine