PMID- 37477250
OWN - NLM
STAT- MEDLINE
DCOM- 20230822
LR  - 20240425
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 36
IP  - 8
DP  - 2023 Aug 21
TI  - Isotope Labeling Mass Spectrometry to Quantify Endogenous and Exogenous DNA 
      Adducts and Metabolites of 1,3-Butadiene In Vivo.
PG  - 1409-1418
LID - 10.1021/acs.chemrestox.3c00141 [doi]
AB  - Human exposure to known carcinogen 1,3-butadiene (BD) is common due to its high 
      concentrations in automobile exhaust, cigarette smoke, and forest fires, as well 
      as its widespread use in the polymer industry. The adverse health effects of BD 
      are mediated by epoxide metabolites such as 3,4-epoxy-1-butene (EB), which reacts 
      with DNA to form 1-hydroxyl-3-buten-1-yl adducts on DNA nucleobases. EB-derived 
      mercapturic acids (1- and 2-(N-acetyl-l-cysteine-S-yl)-1-hydroxybut-3-ene (MHBMA) 
      and N-acetyl-S-(3,4-dihydroxybutyl)-l-cysteine (DHBMA)) and urinary 
      N7-(1-hydroxyl-3-buten-1-yl) guanine DNA adducts (EB-GII) have been used as 
      biomarkers of BD exposure and cancer risk in smokers and occupationally exposed 
      workers. However, low but significant levels of MHBMA, DHBMA, and EB-GII have 
      been reported in unexposed cultured cells, animals, and humans, suggesting that 
      these metabolites and adducts may form endogenously and complicate risk 
      assessment of butadiene exposure. In the present work, stable isotope labeling in 
      combination with high-resolution mass spectrometry was employed to accurately 
      quantify endogenous and exogenous butadiene metabolites and DNA adducts in vivo. 
      Laboratory rats were exposed to 0.3, 0.5, or 3 ppm of BD-d(6) by inhalation, and 
      the amounts of endogenous (d(0)) and exogenous (d(6)) DNA adducts and metabolites 
      were quantified in tissues and urine by isotope dilution capillary liquid 
      chromatography/high resolution electrospray ionization tandem mass spectrometry 
      (capLC-ESI-HRMS/MS). Our results reveal that EB-GII adducts and MHBMA originate 
      exclusively from exogenous exposure to BD, while substantial amounts of DHBMA are 
      formed endogenously. Urinary EB-GII concentrations were associated with genomic 
      EB-GII levels in tissues of the same animals. Our findings confirm that EB-GII 
      and MHBMA are specific biomarkers of exposure to BD, while endogenous DHBMA 
      predominates at sub-ppm exposures to BD.
FAU - Jokipii Krueger, Caitlin C
AU  - Jokipii Krueger CC
AUID- ORCID: 0000-0002-5072-6614
AD  - Masonic Cancer Center and Department of Medicinal Chemistry, University of 
      Minnesota, Minneapolis, Minnesota 55455, United States.
FAU - Moran, Erik
AU  - Moran E
AD  - Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, 
      United States.
FAU - Tessier, Katelyn M
AU  - Tessier KM
AD  - Masonic Cancer Center, Biostatistics Core, University of Minnesota, Minneapolis, 
      Minnesota 55455, United States.
FAU - Tretyakova, Natalia Y
AU  - Tretyakova NY
AUID- ORCID: 0000-0002-0621-6860
AD  - Masonic Cancer Center and Department of Medicinal Chemistry, University of 
      Minnesota, Minneapolis, Minnesota 55455, United States.
LA  - eng
GR  - P01 CA138338/CA/NCI NIH HHS/United States
GR  - P30 CA077598/CA/NCI NIH HHS/United States
GR  - R01 CA100670/CA/NCI NIH HHS/United States
GR  - UL1 TR002494/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230721
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (DNA Adducts)
RN  - JSD5FGP5VD (1,3-butadiene)
RN  - 0 (Butadienes)
RN  - 9007-49-2 (DNA)
RN  - WYQ7N0BPYC (Acetylcysteine)
RN  - 0 (Biomarkers)
RN  - 0 (Epoxy Compounds)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Humans
MH  - *DNA Adducts
MH  - *Butadienes/chemistry
MH  - Isotope Labeling
MH  - Mass Spectrometry/methods
MH  - DNA
MH  - Acetylcysteine/urine
MH  - Biomarkers/urine
MH  - Epoxy Compounds/chemistry
PMC - PMC11009968
MID - NIHMS1981271
COIS- Conflict of Interest Disclosure. The authors declare no competing financial 
      interest.
EDAT- 2023/07/21 13:15
MHDA- 2023/08/22 06:42
PMCR- 2024/08/21
CRDT- 2023/07/21 07:33
PHST- 2024/08/21 00:00 [pmc-release]
PHST- 2023/08/22 06:42 [medline]
PHST- 2023/07/21 13:15 [pubmed]
PHST- 2023/07/21 07:33 [entrez]
AID - 10.1021/acs.chemrestox.3c00141 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2023 Aug 21;36(8):1409-1418. doi: 
      10.1021/acs.chemrestox.3c00141. Epub 2023 Jul 21.