PMID- 27997139
OWN - NLM
STAT- MEDLINE
DCOM- 20170717
LR  - 20211204
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 30
IP  - 2
DP  - 2017 Feb 20
TI  - Isotope Dilution nanoLC/ESI(+)-HRMS(3) Quantitation of Urinary 
      N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers 
      of Exposure to 1,3-Butadiene.
PG  - 678-688
LID - 10.1021/acs.chemrestox.6b00407 [doi]
AB  - 1,3-Butadiene (BD) is an important industrial and environmental chemical 
      classified as a known human carcinogen. Occupational exposure to BD in the 
      polymer and monomer industries is associated with an increased incidence of 
      lymphoma. BD is present in automobile exhaust, cigarette smoke, and forest fires, 
      raising concern about potential exposure of the general population to this 
      carcinogen. Following inhalation exposure, BD is bioactivated to 
      3,4-epoxy-1-butene (EB). If not detoxified, EB is capable of modifying guanine 
      and adenine bases of DNA to form nucleobase adducts, which interfere with 
      accurate DNA replication and cause cancer-initiating mutations. We have developed 
      a nanoLC/ESI(+)-HRMS(3) methodology for N7-(1-hydroxy-3-buten-2-yl) guanine 
      (EB-GII) adducts in human urine (limit of detection: 0.25 fmol/mL urine; limit of 
      quantitation: 1.0 fmol/mL urine). This new method was successfully used to 
      quantify EB-GII in urine of F344 rats treated with 0-200 ppm of BD, 
      occupationally exposed workers, and smokers belonging to two different ethnic 
      groups. EB-GII amounts increased in a dose-dependent manner in urine of 
      laboratory rats exposed to 0, 62.5, or 200 ppm of BD. Urinary EB-GII levels were 
      significantly increased in workers occupationally exposed to 0.1-2.2 ppm of BD 
      (1.25 +/- 0.51 pg/mg of creatinine) as compared to administrative controls exposed 
      to <0.01 ppm of BD (0.22 +/- 0.08 and pg/mg of creatinine) (p = 0.0024), validating 
      the use of EB-GII as a biomarker of human exposure to BD. EB-GII was also 
      detected in smokers' urine with European American smokers excreting significantly 
      higher amounts of EB-GII than African American smokers (0.48 +/- 0.09 vs 0.12 +/- 
      0.02 pg/mg of creatinine, p = 3.1 x 10(-7)). Interestingly, small amounts of 
      EB-GII were observed in animals and humans with no known exposure to BD, 
      providing preliminary evidence for its endogenous formation. Urinary EB-GII 
      adduct levels and urinary mercapturic acids of BD (MHBMA, DHBMA) were compared in 
      a genotyped multiethnic smoker cohort.
FAU - Sangaraju, Dewakar
AU  - Sangaraju D
FAU - Boldry, Emily J
AU  - Boldry EJ
FAU - Patel, Yesha M
AU  - Patel YM
AD  - Division of Biostatistics, Keck School of Medicine and Children's Cancer Group, 
      University of Southern California , Los Angeles, California 90089, United States.
FAU - Walker, Vernon
AU  - Walker V
AD  - Department of Pathology and Laboratory Medicine, University of Vermont , 
      Burlington, Vermont 05405, United States.
FAU - Stepanov, Irina
AU  - Stepanov I
AUID- ORCID: 0000-0001-5140-8944
FAU - Stram, Daniel
AU  - Stram D
AD  - Division of Biostatistics, Keck School of Medicine and Children's Cancer Group, 
      University of Southern California , Los Angeles, California 90089, United States.
FAU - Hatsukami, Dorothy
AU  - Hatsukami D
FAU - Tretyakova, Natalia
AU  - Tretyakova N
AUID- ORCID: 0000-0002-0621-6860
LA  - eng
GR  - P01 CA138338/CA/NCI NIH HHS/United States
GR  - P30 CA077598/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Validation Study
DEP - 20170117
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Biomarkers)
RN  - 0 (Butadienes)
RN  - 0 (N-7-(1-hydroxy-3-buten-2-yl)guanine)
RN  - 5Z93L87A1R (Guanine)
RN  - JSD5FGP5VD (1,3-butadiene)
SB  - IM
MH  - Animals
MH  - Biomarkers/*urine
MH  - Butadienes/*toxicity
MH  - Chromatography, High Pressure Liquid
MH  - Ethnicity
MH  - Guanine/urine
MH  - Humans
MH  - Indicator Dilution Techniques
MH  - Mass Spectrometry/*methods
MH  - Rats
MH  - Rats, Inbred F344
MH  - Reproducibility of Results
MH  - Spectrometry, Mass, Electrospray Ionization/*methods
PMC - PMC5515386
MID - NIHMS874818
COIS- Notes The authors declare no competing financial interest.
EDAT- 2016/12/21 06:00
MHDA- 2017/07/18 06:00
PMCR- 2017/08/20
CRDT- 2016/12/21 06:00
PHST- 2016/12/21 06:00 [pubmed]
PHST- 2017/07/18 06:00 [medline]
PHST- 2016/12/21 06:00 [entrez]
PHST- 2017/08/20 00:00 [pmc-release]
AID - 10.1021/acs.chemrestox.6b00407 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2017 Feb 20;30(2):678-688. doi: 10.1021/acs.chemrestox.6b00407. 
      Epub 2017 Jan 17.