PMID- 30016111
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20200225
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 31
IP  - 9
DP  - 2018 Sep 17
TI  - N(6)-(2-Deoxy-d- erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5- 
      N-(2-hydroxy-3-buten-1-yl)-formamidopyrimidine Adducts of 1,3-Butadiene: 
      Synthesis, Structural Identification, and Detection in Human Cells.
PG  - 885-897
LID - 10.1021/acs.chemrestox.8b00123 [doi]
AB  - 1,3-Butadiene (BD) is an environmental and occupational toxicant classified as a 
      human carcinogen. BD is metabolically activated by cytochrome P450 monooxygenases 
      to 3,4-epoxy-1-butene (EB), which alkylates DNA to form a range of nucleobase 
      adducts. Among these, the most abundant are the hydrolytically labile N7-guanine 
      adducts such as N7-(2-hydroxy-3-buten-1-yl)-guanine (N7-EB-dG). We now report 
      that N7-EB-dG can be converted to the corresponding ring open N(6)-(2-deoxy-d- 
      erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5- 
      N-(2-hydroxy-3-buten-1-yl)-formamidopyrimidine (EB-Fapy-dG) adducts. EB-Fapy-dG 
      lesions were detected in EB-treated calf thymus DNA and in EB-treated mammalian 
      cells using quantitative isotope dilution nanoLC-ESI(+)-MS/MS. EB-Fapy-dG adduct 
      formation in EB-treated calf thymus DNA was concentration dependent and was 
      greatly accelerated at an increased pH. EB-FAPy-dG adduct amounts were 2-fold 
      higher in base excision repair-deficient NEIL1(-/-) mouse embryonic fibroblasts 
      (MEF) as compared to isogenic controls (NEIL1(+/+)), suggesting that this lesion 
      may be a substrate for NEIL1. Furthermore, NEIL1(-/-) cells were sensitized to EB 
      treatment as compared to NEIL1(+/+) fibroblasts. Overall, our results indicate 
      that ring-opened EB-FAPy-dG adducts form under physiological conditions, 
      prompting future studies to determine their contributions to genotoxicity and 
      mutagenicity of BD.
FAU - Groehler, Arnold S 4th
AU  - Groehler AS 4th
AD  - Department of Medicinal Chemistry and Masonic Cancer Center , University of 
      Minnesota , Minneapolis , Minnesota 55455 , United States.
FAU - Najjar, Dominic
AU  - Najjar D
AD  - Department of Medicinal Chemistry and Masonic Cancer Center , University of 
      Minnesota , Minneapolis , Minnesota 55455 , United States.
FAU - Pujari, Suresh S
AU  - Pujari SS
AUID- ORCID: 0000-0002-0246-3362
AD  - Department of Medicinal Chemistry and Masonic Cancer Center , University of 
      Minnesota , Minneapolis , Minnesota 55455 , United States.
FAU - Sangaraju, Dewakar
AU  - Sangaraju D
AD  - Department of Medicinal Chemistry and Masonic Cancer Center , University of 
      Minnesota , Minneapolis , Minnesota 55455 , United States.
FAU - Tretyakova, Natalia Y
AU  - Tretyakova NY
AUID- ORCID: 0000-0002-0621-6860
AD  - Department of Medicinal Chemistry and Masonic Cancer Center , University of 
      Minnesota , Minneapolis , Minnesota 55455 , United States.
LA  - eng
GR  - R01 CA100670/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180904
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Carcinogens)
RN  - 0 (DNA Adducts)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Pyrimidines)
RN  - 478ERR5NKR (3,4-epoxy-1-butene)
RN  - 9007-49-2 (DNA)
RN  - 91080-16-9 (calf thymus DNA)
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (Neil1 protein, mouse)
MH  - Animals
MH  - Carbon-13 Magnetic Resonance Spectroscopy
MH  - Carcinogens/*chemistry/toxicity
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid/methods
MH  - DNA/drug effects/metabolism
MH  - DNA Adducts/analysis/*chemistry
MH  - DNA Glycosylases/genetics
MH  - Dose-Response Relationship, Drug
MH  - Epoxy Compounds/administration & dosage/*chemistry/toxicity
MH  - Indicator Dilution Techniques
MH  - Mice
MH  - Molecular Structure
MH  - Proton Magnetic Resonance Spectroscopy
MH  - Pyrimidines/*chemistry
MH  - Reproducibility of Results
MH  - Spectrometry, Mass, Electrospray Ionization/methods
MH  - Spectrophotometry, Ultraviolet/methods
MH  - Tandem Mass Spectrometry/methods
PMC - PMC6542698
MID - NIHMS1024989
EDAT- 2018/07/18 06:00
MHDA- 2019/07/30 06:00
PMCR- 2019/09/17
CRDT- 2018/07/18 06:00
PHST- 2018/07/18 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2018/07/18 06:00 [entrez]
PHST- 2019/09/17 00:00 [pmc-release]
AID - 10.1021/acs.chemrestox.8b00123 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2018 Sep 17;31(9):885-897. doi: 10.1021/acs.chemrestox.8b00123. 
      Epub 2018 Sep 4.