Work

DNA Interstrand Cross-Linking Activity of (1-Chloroethenyl)oxirane, a Metabolite of β-chloroprene

Year: 2009

Type: article

Abstract: With the goal of elucidating the molecular and cellular mechanisms of chloroprene toxicity, we examined the potential DNA cross-linking of the bifunctional chloroprene metabolite, (1-chloroethenyl)oxirane (CEO). We used denaturing polyacrylamide gel electrophoresis to monitor the possible formation of interstrand cross-links by CEO within synthetic DNA duplexes. Our data suggest interstrand cross-linking at deoxyguanosine residues within 5'-GC and 5'-GGC sites, with the rate of cross-linking depending on pH (pH 5.0 > pH 6.0 > pH 7.0). A comparison of the cross-linking efficiencies of CEO and the structurally similar cross-linkers diepoxybutane (DEB) and epichlorohydrin (ECH) revealed that DEB > CEO > or = ECH. Furthermore, we found that cytotoxicity correlates with cross-linking efficiency, supporting a role for interstrand cross-links in the genotoxicology of chloroprene.

Source: Chemical Research in Toxicology

DOI: 10.1021/tx9003769

Authors: Brian A. Wadugu, Christopher Ng, Bethany L. Bartley, Rebecca J. Rowe, Julie T. Millard

Institutions: Colby College, University of Maine

Language: English

Topic: Carcinogens and Genotoxicity Assessment

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Center for Research Resources

Awards: Comparative Functional Genomics INBRE in Maine, G634933097