PMID- 16698003
OWN - NLM
STAT- MEDLINE
DCOM- 20070523
LR  - 20181016
IS  - 0009-2797 (Print)
IS  - 0009-2797 (Linking)
VI  - 166
IP  - 1-3
DP  - 2007 Mar 20
TI  - Some insights into the mode of action of butadiene by examining the genotoxicity 
      of its metabolites.
PG  - 132-9
AB  - 1,3-Butadiene (BTD) is an important commodity chemical and air pollutant that has 
      been shown to be a potent carcinogen in mice, and to a lesser extent, a 
      carcinogen in rats. To better assess butadiene's carcinogenic risk to humans, it 
      is important to understand its mode of action and how this relates to differences 
      in responses among species. In a series of in vitro experiments, lymphocytes from 
      rats, mice, and humans were exposed to 3,4-epoxy-1-butene (EB) or 
      1,2:3,4-diepoxybutane (DEB) for 1h at the G(0) stage of the cell cycle, 
      stimulated to divide, and cultured to assess the ability of these metabolites to 
      induce sister chromatid exchange (SCE) and chromosome aberrations (CAs). EB 
      induced no increases in SCEs or CAs in the cells from the three species. DEB was 
      a potent SCE- and CA-inducer, with the results being similar in each rodent 
      species. The response for SCEs seen in the human cells was more complex, with 
      genetic polymorphism for glutathione-S-transferases (GST) possibly modulating the 
      response. The single cell gel electrophoresis assay was used on genetically 
      engineered V79 cell lines to investigate a possible influence of GST status. 
      Experiments were also conducted to investigate the reason for EB's failure to 
      induce SCEs or CAs in G(0) cells. The results indicate that EB-induced DNA damage 
      was repaired before DNA synthesis in unstimulated lymphocytes, but EB caused a 
      large increase in SCEs if actively cycling cells were treated. Thus, the results 
      indicate that DEB damage is persistent in G(0) cells, and DEB is a much more 
      potent genotoxicant than EB. The carcinogenic effect of butadiene will most 
      likely depend on the degree to which DEB is produced and reaches target tissues, 
      and to a lesser extent on the ability of EB to reach actively dividing or repair 
      deficient cells.
FAU - Kligerman, A D
AU  - Kligerman AD
AD  - B143-06, Cellular Toxicology Branch, Environmental Carcinogenesis Division, 
      National Health and Environmental Effects Research Laboratory, U.S. Environmental 
      Protection Agency, Research Triangle Park, NC 27711, USA. 
      kligerman.andrew@epa.gov
FAU - Hu, Y
AU  - Hu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060418
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Butadienes)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Mutagens)
RN  - 478ERR5NKR (3,4-epoxy-1-butene)
RN  - 60OB65YNAB (diepoxybutane)
RN  - EC 2.5.1.- (glutathione S-transferase T1)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Butadienes/*metabolism/*toxicity
MH  - Cell Cycle/drug effects
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Chromosome Aberrations/drug effects
MH  - DNA Damage/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Epoxy Compounds/*metabolism/*toxicity
MH  - Glutathione/metabolism
MH  - Glutathione Transferase/metabolism
MH  - Humans
MH  - Lymphocytes/drug effects/enzymology
MH  - Mice
MH  - Mutagens/metabolism/toxicity
MH  - Rats
MH  - Resting Phase, Cell Cycle/drug effects
MH  - Sister Chromatid Exchange/drug effects
EDAT- 2006/05/16 09:00
MHDA- 2007/05/24 09:00
CRDT- 2006/05/16 09:00
PHST- 2006/01/19 00:00 [received]
PHST- 2006/03/07 00:00 [revised]
PHST- 2006/03/31 00:00 [accepted]
PHST- 2006/05/16 09:00 [pubmed]
PHST- 2007/05/24 09:00 [medline]
PHST- 2006/05/16 09:00 [entrez]
AID - S0009-2797(06)00076-7 [pii]
AID - 10.1016/j.cbi.2006.03.013 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2007 Mar 20;166(1-3):132-9. doi: 10.1016/j.cbi.2006.03.013. 
      Epub 2006 Apr 18.