PMID- 10567028
OWN - NLM
STAT- MEDLINE
DCOM- 20000308
LR  - 20190513
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 14
IP  - 6
DP  - 1999 Nov
TI  - Evaluation of micronuclei and chromosomal breakage in the 1cen-q12 region by the 
      butadiene metabolites epoxybutene and diepoxybutane in cultured human 
      lymphocytes.
PG  - 541-6
AB  - 1,3-Butadiene is a widely used industrial chemical and common environmental 
      pollutant that has been associated with increased risks of leukemias and 
      lymphomas. Butadiene and its metabolites, 1, 2-epoxybutene (EB) and diepoxybutane 
      (DEB), have been shown to be genotoxic in a wide variety of test organisms. The 
      objective of this research was to evaluate techniques for the rapid detection of 
      chromosomal alterations occurring in humans exposed to butadiene. We have used a 
      multicolored fluorescence in situ hybridization (FISH) method and the 
      CREST-modified micronucleus assay to detect chromosomal breakage induced by EB 
      (10-300 microM) and DEB (0.5-10 microM) in cultured human lymphocytes. A 
      significant dose-related increase in the formation of micronuclei was seen in 
      lymphocytes treated with DEB at concentrations as low as 2.5 microM, but not with 
      EB over the dose range tested. Over 80% of the micronuclei induced by DEB were 
      CREST-negative, indicating their origin from chromosomal breakage. Multicolor 
      FISH using two adjacent chromosome-specific probes showed a significant increase 
      in chromosomal breakage in the 1cen-q12 region induced by DEB at concentrations 
      as low as 2.5 microM, but not by EB. Since DEB is likely to be one of the 
      metabolites contributing to the genotoxic effects of butadiene, the sensitivity 
      of the tandem FISH approach to detect breakage induced by diepoxybutane indicates 
      that this technique may be useful for monitoring chromosomal alterations in 
      butadiene-exposed workers.
FAU - Murg, M n
AU  - Murg Mn
AD  - Environmental Toxicology Graduate Program, University of California, Riverside, 
      CA 92521, USA.
FAU - Schuler, M
AU  - Schuler M
FAU - Eastmond, D A
AU  - Eastmond DA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Butadienes)
RN  - 0 (Carcinogens)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Mutagens)
RN  - 478ERR5NKR (3,4-epoxy-1-butene)
RN  - 60OB65YNAB (diepoxybutane)
SB  - IM
MH  - Butadienes/*metabolism
MH  - Carcinogens/metabolism/pharmacology
MH  - Cells, Cultured
MH  - Centromere/drug effects
MH  - *Chromosome Breakage
MH  - *Chromosomes, Human, Pair 1
MH  - Chromosomes, Human, Pair 9
MH  - Dose-Response Relationship, Drug
MH  - Epoxy Compounds/*toxicity
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Kinetochores/metabolism
MH  - Lymphocytes/*drug effects
MH  - Male
MH  - *Micronucleus Tests
MH  - Mutagens/*toxicity
MH  - Polymerase Chain Reaction/methods
EDAT- 1999/11/24 09:00
MHDA- 2000/03/11 09:00
CRDT- 1999/11/24 09:00
PHST- 1999/11/24 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 1999/11/24 09:00 [entrez]
AID - 10.1093/mutage/14.6.541 [doi]
PST - ppublish
SO  - Mutagenesis. 1999 Nov;14(6):541-6. doi: 10.1093/mutage/14.6.541.