PMID- 23937706
OWN - NLM
STAT- MEDLINE
DCOM- 20140526
LR  - 20211021
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 26
IP  - 10
DP  - 2013 Oct 21
TI  - Capillary HPLC-accurate mass MS/MS quantitation of 
      N7-(2,3,4-trihydroxybut-1-yl)-guanine adducts of 1,3-butadiene in human leukocyte 
      DNA.
PG  - 1486-97
LID - 10.1021/tx400213m [doi]
AB  - 1,3-Butadiene (BD) is a high volume industrial chemical commonly used in polymer 
      and rubber production. It is also present in cigarette smoke, automobile exhaust, 
      and urban air, leading to widespread exposure of human populations. Upon entering 
      the body, BD is metabolized to electrophilic epoxides, 3,4-epoxy-1-butene (EB), 
      diepoxybutane (DEB), and 3,4-epoxy-1,2-diol (EBD), which can alkylate DNA 
      nucleobases. The most abundant BD epoxide, EBD, modifies the N7-guanine positions 
      in DNA to form N7-(2, 3, 4-trihydroxybut-1-yl) guanine (N7-THBG) adducts, which 
      can be useful as biomarkers of BD exposure and metabolic activation to 
      DNA-reactive epoxides. In the present work, a capillary HPLC-high resolution 
      ESI(+)-MS/MS (HPLC-ESI(+)-HRMS/MS) methodology was developed for accurate, sensitive, 
      and reproducible quantification of N7-THBG in cell culture and in human white 
      blood cells. In our approach, DNA is subjected to neutral thermal hydrolysis to 
      release N7-guanine adducts from the DNA backbone, followed by ultrafiltration, 
      solid-phase extraction, and isotope dilution HPLC-ESI(+)-HRMS/MS analysis on an 
      Orbitrap Velos mass spectrometer. Following method validation, N7-THBG was 
      quantified in human fibrosarcoma (HT1080) cells treated with micromolar 
      concentrations of DEB and in DNA isolated from blood of smokers, nonsmokers, 
      individuals participating in a smoking cessation program, and occupationally 
      exposed workers. N7-THBG concentrations increased linearly from 31.4 +/- 4.84 to 
      966.55 +/- 128.05 adducts per 10(9) nucleotides in HT1080 cells treated with 1-100 muM 
      DEB. N7-THBG amounts in leukocyte DNA of nonsmokers, smokers, and occupationally 
      exposed workers were 7.08 +/- 5.29, 8.20 +/- 5.12, and 9.72 +/- 3.80 adducts per 10(9) 
      nucleotides, respectively, suggesting the presence of an endogenous or 
      environmental source for this adduct. The availability of sensitive 
      HPLC-ESI(+)-HRMS/MS methodology for BD-induced DNA adducts in humans will enable 
      future population studies of interindividual and ethnic differences in BD 
      bioactivation to DNA-reactive epoxides.
FAU - Sangaraju, Dewakar
AU  - Sangaraju D
AD  - Department of Medicinal Chemistry and the Masonic Cancer Center, University of 
      Minnesota , Minneapolis, Minnesota 55455, United States.
FAU - Villalta, Peter
AU  - Villalta P
FAU - Goggin, Melissa
AU  - Goggin M
FAU - Agunsoye, Maria O
AU  - Agunsoye MO
FAU - Campbell, Colin
AU  - Campbell C
FAU - Tretyakova, Natalia
AU  - Tretyakova N
LA  - eng
GR  - S10 RR024618/RR/NCRR NIH HHS/United States
GR  - HHSN261200644002/PHS HHS/United States
GR  - P01 CA138338/CA/NCI NIH HHS/United States
GR  - R01 CA100670/CA/NCI NIH HHS/United States
GR  - P30 CA077598/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130912
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Biomarkers)
RN  - 0 (Butadienes)
RN  - 0 (DNA Adducts)
RN  - 0 (N7-(2,3,4-trihydroxybut-1-yl)-guanine)
RN  - 5Z93L87A1R (Guanine)
RN  - 9007-49-2 (DNA)
RN  - JSD5FGP5VD (1,3-butadiene)
SB  - IM
MH  - Adult
MH  - Biomarkers/analysis
MH  - Butadienes/*chemistry
MH  - Cell Line, Tumor
MH  - *Chromatography, High Pressure Liquid
MH  - DNA/*chemistry/metabolism
MH  - DNA Adducts/*analysis
MH  - Female
MH  - Guanine/*analogs & derivatives/chemistry
MH  - Humans
MH  - Leukocytes/metabolism
MH  - Male
MH  - Middle Aged
MH  - Smoking
MH  - *Spectrometry, Mass, Electrospray Ionization
MH  - Young Adult
PMC - PMC3907265
MID - NIHMS524013
EDAT- 2013/08/14 06:00
MHDA- 2014/05/27 06:00
PMCR- 2014/10/21
CRDT- 2013/08/14 06:00
PHST- 2013/08/14 06:00 [entrez]
PHST- 2013/08/14 06:00 [pubmed]
PHST- 2014/05/27 06:00 [medline]
PHST- 2014/10/21 00:00 [pmc-release]
AID - 10.1021/tx400213m [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2013 Oct 21;26(10):1486-97. doi: 10.1021/tx400213m. Epub 2013 
      Sep 12.