DNA interstrand cross-linking activity of (1-Chloroethenyl)oxirane, a metabolite of beta-chloroprene
Wadugu, BA; Ng, C; Bartley, BL; Rowe, RJ; Millard, JT
HERO ID
1508892
Reference Type
Journal Article
Year
2010
Language
English
PMID
| HERO ID | 1508892 |
|---|---|
| In Press | No |
| Year | 2010 |
| Title | DNA interstrand cross-linking activity of (1-Chloroethenyl)oxirane, a metabolite of beta-chloroprene |
| Authors | Wadugu, BA; Ng, C; Bartley, BL; Rowe, RJ; Millard, JT |
| Journal | Chemical Research in Toxicology |
| Volume | 23 |
| Issue | 1 |
| Page Numbers | 235-239 |
| 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. |
| Doi | 10.1021/tx9003769 |
| Pmid | 20030381 |
| Wosid | WOS:000273618500027 |
| Url | <Go to ISI>://WOS:000273618500027 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |