PMID- 34678943
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231213
IS  - 2305-6304 (Electronic)
IS  - 2305-6304 (Linking)
VI  - 9
IP  - 10
DP  - 2021 Oct 2
TI  - Quantitative NanoLC/NSI(+)-HRMS Method for 1,3-Butadiene Induced bis-N7-guanine 
      DNA-DNA Cross-Links in Urine.
LID - 10.3390/toxics9100247 [doi]
LID - 247
AB  - 1,3-Butadiene (BD) is a common environmental and industrial chemical widely used 
      in plastic and rubber manufacturing and also present in cigarette smoke and 
      automobile exhaust. BD is classified as a known human carcinogen based on 
      evidence of carcinogenicity in laboratory animals treated with BD by inhalation 
      and epidemiological studies revealing an increased risk of leukemia and 
      lymphohematopoietic cancers in workers occupationally exposed to BD. Upon 
      exposure via inhalation, BD is bioactivated to several toxic epoxides including 
      3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol (EBD), and 
      1,2,3,4-diepoxybutane (DEB); these are conjugated with glutathione and excreted 
      as 
      2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene 
      (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 
      1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA). Exposure to DEB 
      generates monoalkylated DNA adducts, DNA-DNA crosslinks, and DNA-protein 
      crosslinks, which can cause base substitutions, genomic rearrangements, and large 
      genomic deletions. In this study, we developed a quantitative nanoLC/NSI(+)-HRMS 
      methodology for 1,4-bis-(gua-7-yl)-2,3-butanediol (bis-N7G-BD) adducts in urine 
      (LOD: 0.1 fmol/mL urine, LOQ: 1.0 fmol/mL urine). This novel method was used to 
      quantify bis-N7G-BD in urine of mice treated with 590 +/- 150 ppm BD for 2 weeks (6 
      h/day, 5 days/week). Bis-N7G-BD was detected in urine of male and female 
      BD-exposed mice (574.6 +/- 206.0 and 571.1 +/- 163.4 pg/mg of creatinine, 
      respectively). In addition, major urinary metabolites of BD, bis-BDMA, MHBMA and 
      DHBMA, were measured in the same samples. Urinary bis-N7G-BD adduct levels 
      correlated with DEB-derived metabolite bis-BDMA (r = 0.80, Pearson correlation), 
      but not with the EB-derived DNA adducts (EB-GII) or EB-derived metabolites MHBMA 
      and DHBMA (r = 0.24, r = 0.14, r = 0.18, respectively, Pearson correlations). 
      Urinary bis-N7G-BD could be employed as a novel non-invasive biomarker of 
      exposure to BD and bioactivation to its most mutagenic metabolite, DEB. This 
      method will be useful for future studies of 1,3-butadiene exposure and 
      metabolism.
FAU - Erber, Luke
AU  - Erber L
AUID- ORCID: 0000-0001-5527-5501
AD  - Department of Medicinal Chemistry and Masonic Cancer Center, University of 
      Minnesota, Minneapolis, MN 55455, USA.
FAU - Goodman, Samantha
AU  - Goodman S
AD  - Department of Veterinary Integrative Biosciences, College of Veterinary Medicine 
      and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
FAU - Jokipii Krueger, Caitlin C
AU  - Jokipii Krueger CC
AD  - Department of Medicinal Chemistry and Masonic Cancer Center, University of 
      Minnesota, Minneapolis, MN 55455, USA.
FAU - Rusyn, Ivan
AU  - Rusyn I
AD  - Department of Veterinary Integrative Biosciences, College of Veterinary Medicine 
      and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
FAU - Tretyakova, Natalia
AU  - Tretyakova N
AUID- ORCID: 0000-0002-0621-6860
AD  - Department of Medicinal Chemistry and Masonic Cancer Center, University of 
      Minnesota, Minneapolis, MN 55455, USA.
LA  - eng
GR  - R01 CA100670/CA/NCI NIH HHS/United States
GR  - T32 ES026568/ES/NIEHS NIH HHS/United States
GR  - 5K12GM119955/GM/NIGMS NIH HHS/United States
GR  - K12 GM119955/GM/NIGMS NIH HHS/United States
GR  - R01 ES029911/ES/NIEHS NIH HHS/United States
GR  - P01 CA138338/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20211002
PL  - Switzerland
TA  - Toxics
JT  - Toxics
JID - 101639637
PMC - PMC8540193
OTO - NOTNLM
OT  - 1,3-butadiene
OT  - LC-MS/MS
OT  - bis-N7G-BD
OT  - mercapturic acids
OT  - urinary DNA adducts
COIS- The authors declare no conflict of interest.
EDAT- 2021/10/23 06:00
MHDA- 2021/10/23 06:01
PMCR- 2021/10/02
CRDT- 2021/10/22 21:02
PHST- 2021/08/19 00:00 [received]
PHST- 2021/09/13 00:00 [revised]
PHST- 2021/09/28 00:00 [accepted]
PHST- 2021/10/22 21:02 [entrez]
PHST- 2021/10/23 06:00 [pubmed]
PHST- 2021/10/23 06:01 [medline]
PHST- 2021/10/02 00:00 [pmc-release]
AID - toxics9100247 [pii]
AID - toxics-09-00247 [pii]
AID - 10.3390/toxics9100247 [doi]
PST - epublish
SO  - Toxics. 2021 Oct 2;9(10):247. doi: 10.3390/toxics9100247.