Carcinogenesis, Vol 18, 1687-1693, Copyright © 1997 by Oxford University Press
L Xi, L Zhang, Y Wang and MT Smith
1,3-Butadiene is a carcinogen in rodents, but its potential carcinogenicity
to humans remains controversial. Numerous studies have shown that butadiene
and its metabolites cause sister chromatid exchanges in vitro and in vivo.
To test for other types of genotoxicity, the micronucleus assay and
fluorescence in situ hybridization (FISH) have been used to detect
chromosome damage in human lymphocytes caused by two reactive metabolites
of butadiene, diepoxybutane (DEB) and monoepoxybutene (MEB). DEB (0.5-5.0
microM) significantly increased micronucleus formation 4- to 6-fold (P
<0.01) and MEB (1-500 microM) by 2- to 4-fold (P <0.01) over control
levels. The ability of DEB and MEB to induce aneuploidy of chromosomes 7,
8, 12, and X was examined using dual-color FISH in both interphase and
metaphase cells. These chromosomes were chosen because of their involvement
in leukemogenesis. Both DEB and MEB caused dose-dependent increases in
hyperdiploidy of chromosomes 12 and X, but had no discernible effect on
chromosomes 7 and 8. These results suggest that DEB and MEB cause
chromosome-specific aneuploidy in human cells. If formed in sufficient
amounts, DEB and MEB may produce chromosome damage of the type found in
leukemia following exposure to butadiene.
ARTICLES
Induction of chromosome-specific aneuploidy and micronuclei in human lymphocytes by metabolites of 1,3-butadiene
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720-7360, USA.
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