PMID- 14680375
OWN - NLM
STAT- MEDLINE
DCOM- 20040429
LR  - 20181016
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 16
IP  - 12
DP  - 2003 Dec
TI  - Identification and characterization of a series of nucleoside adducts formed by 
      the reaction of 2'-deoxyguanosine and 1,2,3,4-diepoxybutane under physiological 
      conditions.
PG  - 1606-15
AB  - The carcinogenicity of 1,3-butadiene (BD) has been attributed to its in vivo 
      metabolites, 3,4-epoxy-1-butene (EB) and 1,2,3,4-diepoxybutane (DEB). In this 
      study, DEB was demonstrated to react with 2'-deoxyguanosine (dG) under in vitro 
      physiological conditions (pH 7.4, 37 degrees C) to yield several pairs of 
      diastereomeric adducts, including N-(2-hydroxy-1-oxiranylethyl)-2'-deoxyguanosine 
      (P4-1 and P4-2), 
      7,8-dihydroxy-3-(2-deoxy-beta-d-erythro-pentofuranosyl)-3,5,6,7,8,9-hexahydro-1,3-diazepino[1,2-a]purin-11(11H)one 
      (P6), 1-(2-hydroxy-2-oxiranylethyl)-2'-deoxyguanosine (P8 and P9), 
      1-[3-chloro-2-hydroxy-1-(hydroxymethyl)propyl]-2'-deoxyguanosine (1AP9 and 2AP9), 
      and 
      4,8-dihydroxy-1-(2-deoxy-beta-d-erythro-pentofuranosyl)-9-hydroxymethyl-6,7,8,9-tetrahydro-1H-pyrimido[2,1-b]purinium 
      ion (1BP4 and 2BP4). The 7-alkylation dG adducts (P5 and P5') were not 
      characterized directly by NMR spectrometry because of their instability. However, 
      their formula weights were determined to be 354, and their acid hydrolysis 
      products were characterized as 
      2-amino-7-(3-chloro-2,4-dihydroxybutyl)-1,7-dihydro-6H-purin-6-one (H3), 
      consistent with the structures of P5 and P5' being diastereomers of 
      6-oxo-2-amino-9-(2-deoxy-beta-d-erythro-pentofuranosyl)-7-(2-hydroxy-2-oxiranylethyl)-6,9-dihydro-1H-purinium 
      ion. Time-course experiments indicated that alkaline pH and/or high DEB:dG molar 
      ratios made the reactions faster without changing the adduct profile. The adducts 
      were detected in the following chronological order: 7- (P5 and P5'), 1- (P8 and 
      P9), N(2)- (P4-1 and P4-2), and P6. Whereas P4-1, P4-2, and P6 appeared stable 
      during the courses of the reactions, P5, P5', P8, and P9 were labile and 
      completely decomposed by the time dG was fully consumed. These results may 
      contribute to a better understanding of the chemical reactivity and strong 
      mutagenicity and carcinogenicity of DEB.
FAU - Zhang, Xin-Yu
AU  - Zhang XY
AD  - Department of Comparative Biosciences and the Molecular and Environmental 
      Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin 53706, 
      USA.
FAU - Elfarra, Adnan A
AU  - Elfarra AA
LA  - eng
GR  - GM66326/GM/NIGMS NIH HHS/United States
GR  - RR02301/RR/NCRR NIH HHS/United States
GR  - RR02781/RR/NCRR NIH HHS/United States
GR  - RR08438/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Epoxy Compounds)
RN  - 0 (Nucleosides)
RN  - 60OB65YNAB (diepoxybutane)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - Alkylation
MH  - Chromatography, High Pressure Liquid
MH  - Deoxyguanosine/*analogs & derivatives/*chemistry
MH  - Epoxy Compounds/*chemistry
MH  - Hydrogen-Ion Concentration
MH  - Kinetics
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Nucleosides/chemistry
EDAT- 2003/12/19 05:00
MHDA- 2004/04/30 05:00
CRDT- 2003/12/19 05:00
PHST- 2003/12/19 05:00 [pubmed]
PHST- 2004/04/30 05:00 [medline]
PHST- 2003/12/19 05:00 [entrez]
AID - 10.1021/tx0341355 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2003 Dec;16(12):1606-15. doi: 10.1021/tx0341355.