PMID- 32237725
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20240402
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 33
IP  - 7
DP  - 2020 Jul 20
TI  - Interindividual Differences in DNA Adduct Formation and Detoxification of 
      1,3-Butadiene-Derived Epoxide in Human HapMap Cell Lines.
PG  - 1698-1708
LID - 10.1021/acs.chemrestox.9b00517 [doi]
AB  - Smoking-induced lung cancer is a major cause of cancer mortality in the US and 
      worldwide. While 11-24% of smokers will develop lung cancer, risk varies among 
      individuals and ethnic/racial groups. Specifically, African American and Native 
      Hawaiian cigarette smokers are more likely to get lung cancer as compared to 
      Caucasians, Japanese Americans, and Latinos. It is important to identify smokers 
      who are at the greatest risk of developing lung cancer as they should be 
      candidates for smoking cessation and chemopreventive intervention programs. Among 
      60+ tobacco smoke carcinogens, 1,3-butadiene (BD) is one of the most potent and 
      abundant (20-75 mug per cigarette in mainstream smoke and 205-361 mug per cigarette 
      in side stream smoke). BD is metabolically activated to 3,4-epoxy-1-butene (EB), 
      which can be detoxified by glutathione S-transferase theta 1 (GSTT1)-mediated 
      conjugation with glutathione, or can react with DNA to form 
      7-(1-hydroxy-3-buten-2-yl)guanine (EB-GII) adducts. In the present study, we 
      employed EBV-transformed human lymphoblastoid cell lines (HapMap cells) with 
      known GSTT1 genotypes to examine the influence of the GSTT1 gene on 
      interindividual variability in butadiene metabolism, DNA adduct formation/repair, 
      and biological outcomes (apoptosis). We found that GSTT1(-) HapMap cells treated 
      with EB in culture produced lower levels of glutathione conjugates and were more 
      susceptible to apoptosis but had similar numbers of EB-GII adducts as GSTT1(+) 
      cells. Our results suggest that GSTT1 can influence an individual's 
      susceptibility to butadiene-derived epoxides.
FAU - Degner, Amanda
AU  - Degner A
AD  - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, 
      Minnesota 55455, United States.
AD  - Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, 2-147 CCRB, 
      Minneapolis, Minnesota 55455, United States.
FAU - Arora, Rashi
AU  - Arora R
AD  - Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, 2-147 CCRB, 
      Minneapolis, Minnesota 55455, United States.
FAU - Erber, Luke
AU  - Erber L
AD  - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, 
      Minnesota 55455, United States.
AD  - Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, 2-147 CCRB, 
      Minneapolis, Minnesota 55455, United States.
FAU - Chao, Christopher
AU  - Chao C
AD  - Department of Medicinal Chemistry, University of Minnesota, Minneapolis, 
      Minnesota 55455, United States.
AD  - Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, 2-147 CCRB, 
      Minneapolis, Minnesota 55455, United States.
FAU - Peterson, Lisa A
AU  - Peterson LA
AUID- ORCID: 0000-0001-8715-4480
AD  - Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, 2-147 CCRB, 
      Minneapolis, Minnesota 55455, United States.
AD  - Division of Environmental Health Sciences, 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, University of Minnesota, Minneapolis, 
      Minnesota 55455, United States.
AD  - Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, 2-147 CCRB, 
      Minneapolis, Minnesota 55455, United States.
LA  - eng
GR  - P01 CA138338/CA/NCI NIH HHS/United States
GR  - R01 CA100670/CA/NCI NIH HHS/United States
GR  - R01 ES029911/ES/NIEHS NIH HHS/United States
GR  - S10 OD021536/OD/NIH HHS/United States
PT  - Journal Article
DEP - 20200415
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Butadienes)
RN  - 0 (DNA Adducts)
RN  - 0 (Epoxy Compounds)
RN  - 5Z93L87A1R (Guanine)
RN  - EC 2.5.1.- (glutathione S-transferase T1)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - JSD5FGP5VD (1,3-butadiene)
SB  - IM
MH  - Apoptosis
MH  - Butadienes/chemistry/*metabolism
MH  - Cell Line
MH  - DNA Adducts/*biosynthesis
MH  - DNA Repair
MH  - Epoxy Compounds/chemistry/*metabolism
MH  - Glutathione Transferase/deficiency/genetics/*metabolism
MH  - Guanine/analogs & derivatives/*biosynthesis
MH  - *Haplotypes
MH  - Humans
MH  - Molecular Structure
PMC - PMC8177104
MID - NIHMS1606825
COIS- The authors declare no competing financial interest.
EDAT- 2020/04/03 06:00
MHDA- 2021/07/02 06:00
PMCR- 2021/07/20
CRDT- 2020/04/03 06:00
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/04/03 06:00 [entrez]
PHST- 2021/07/20 00:00 [pmc-release]
AID - 10.1021/acs.chemrestox.9b00517 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2020 Jul 20;33(7):1698-1708. doi: 
      10.1021/acs.chemrestox.9b00517. Epub 2020 Apr 15.