TOXI 130 |
| 1,2,3,4-diepoxybutane (DEB) is the suspected carcinogenic species of 1,3-butadiene (BD), a major industrial chemical recognized as a human carcinogen. DEB is the most genotoxic metabolite of BD, probably because of its ability to form bifunctional DNA and protein adducts by sequential alkylation of two nucleophilic sites within cellular biomolecules. Our laboratory employed a combination of organic synthesis, NMR spectroscopy, gel electrophoresis, and capillary HPLC-ESI-MS/MS to characterize DEB induced DNA-DNA adducts and to detect their formation in vivo. Both guanine-guanine and guanine-adenine conjugates were isolated from DEB-treated calf thymus DNA. In addition, DEB produced exocyclic 1,N6-BD-dA and N6,N6-BD-dA adducts. Quantitative HPLC-ESI-MS/MS methods were developed for measuring the predominant DNA-DNA cross-links of DEB, bis-N7G-BD, and exocyclic dA adducts in DNA extracted from BD-exposed laboratory animals. DNA extracted from liver and lung tissues of mice exposed to BD contained bis-N7G-BD and exocyclic dA adducts, while control animals did not contain either lesion.
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General Papers
1:00 PM-4:45 PM, Wednesday, August 22, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |
