PMID- 22698567
OWN - NLM
STAT- MEDLINE
DCOM- 20120918
LR  - 20181016
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 747
IP  - 2
DP  - 2012 Sep 18
TI  - DNA damage induced by three major metabolites of 1,3-butadiene in human 
      hepatocyte L02 cells.
PG  - 240-5
LID - 10.1016/j.mrgentox.2012.06.001 [doi]
AB  - 1,3-Butadiene (BD) is a carcinogenic air pollutant. Its bioactivation produces 
      four major metabolites, i.e., 3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol 
      (EBD), 1,2,3,4-diepoxybutane (DEB), and 3-butene-1,2-diol (BDD). Studies have 
      been mostly focused on DEB due to its strong mutagenicity/carcinogenicity. In 
      contrast, studies of genotoxicity of EB, EBD, and BDD have been limited. In 
      particular, genotoxicity of EBD and BDD using strand breaks as the endpoint has 
      not been investigated. To obtain a more complete understanding of BD toxicity, in 
      the present study, we used comet assay to investigate DNA damage induced by EB, 
      EBD, and BDD in human hepatocyte L02 cells, with the aim to determine their 
      relative potencies, the types of DNA damage, and the possible pathway to form 
      strand breaks. Using alkaline comet assay (pH>13), it was observed that EB and 
      EBD caused similar concentration-dependent increases in DNA migration from 50 to 
      1000muM. However, BDD induced a statistically significant increase only at 1000muM, 
      and the increase itself was very small. EBD was as potent as EB at lower 
      concentrations (</=200muM), and was slightly less potent than EB at higher 
      concentrations. The results indicated that these metabolites could generate 
      strand breaks in cells with the rank order of the potencies being EB> approximately EBD>>BDD. 
      All three compounds failed to cause statistically significant increases in DNA 
      migration in pre-lysed cells, suggesting that they did not produce strand breaks 
      through chemical pathways under our experimental conditions. By using comet 
      assays at pH 11.9 and pH 9, it was demonstrated that EB and EBD generated both 
      single-strand breaks (SSB) and alkali-labile sites, but BDD produced only SSB. To 
      our knowledge, this is the first report to investigate EBD- and BDD-induced 
      strand breaks in cells. The results implied that EBD could play an important role 
      in toxicity of BD.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Zhang, Pan-Pan
AU  - Zhang PP
AD  - School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 
      People's Republic of China.
FAU - Wen, Ying
AU  - Wen Y
FAU - An, Jing
AU  - An J
FAU - Yu, Ying-Xin
AU  - Yu YX
FAU - Wu, Ming-Hong
AU  - Wu MH
FAU - Zhang, Xin-Yu
AU  - Zhang XY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120612
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (3,4-epoxy-1,2-butanediol)
RN  - 0 (Butadienes)
RN  - 0 (Butylene Glycols)
RN  - 0 (Carcinogens)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Mutagens)
RN  - 478ERR5NKR (3,4-epoxy-1-butene)
RN  - 60OB65YNAB (diepoxybutane)
RN  - JSD5FGP5VD (1,3-butadiene)
SB  - IM
MH  - Butadienes/*metabolism
MH  - Butylene Glycols/*toxicity
MH  - Carcinogens/*toxicity
MH  - Cell Line, Transformed
MH  - Comet Assay
MH  - DNA Breaks, Single-Stranded
MH  - *DNA Damage
MH  - Epoxy Compounds/*toxicity
MH  - Hepatocytes/*drug effects
MH  - Humans
MH  - Mutagens/*therapeutic use/*toxicity
EDAT- 2012/06/16 06:00
MHDA- 2012/09/19 06:00
CRDT- 2012/06/16 06:00
PHST- 2011/11/25 00:00 [received]
PHST- 2012/04/24 00:00 [revised]
PHST- 2012/06/02 00:00 [accepted]
PHST- 2012/06/16 06:00 [entrez]
PHST- 2012/06/16 06:00 [pubmed]
PHST- 2012/09/19 06:00 [medline]
AID - S1383-5718(12)00201-X [pii]
AID - 10.1016/j.mrgentox.2012.06.001 [doi]
PST - ppublish
SO  - Mutat Res. 2012 Sep 18;747(2):240-5. doi: 10.1016/j.mrgentox.2012.06.001. Epub 
      2012 Jun 12.