Characterization and Quantitative Analysis of DNA Adducts Formed from Lower Chlorinated PCB-Derived Quinones
| Autor: | George Eadon, Xinxin Ding, Amarjit Narang, Shouxun Zhao |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
chemistry.chemical_classification
Catechol Quinones Guanosine General Medicine Toxicology Polychlorinated Biphenyls Mass Spectrometry Adduct DNA Adducts chemistry.chemical_compound chemistry DNA adduct Organic chemistry Environmental Pollutants Nucleotide DNA Adduction Oxidation-Reduction Phosphorus Radioisotopes Quantitative analysis (chemistry) Chromatography High Pressure Liquid DNA |
| Zdroj: | Chemical Research in Toxicology. 17:502-511 |
| ISSN: | 1520-5010 0893-228X |
| Popis: | Polychlorinated biphenyls are wide pollutants readily detected in environmental and human specimens. DNA adduction occurs through the corresponding quinones. Polychlorinated biphenyls are first metabolized to arene oxides, which can be further oxidized to dihydroxy metabolites by microsomal cytochrome P450s. The catechol and hydroquinone products are further oxidized by peroxidases to quinones, which are electrophilic and capable of reacting with DNA to form adducts. DNA adduction is initiated by Michael addition preferentially to guanosine followed by stabilization through enolization. Another nucleophilic attack forms a five-membered ring, which aromatizes by dehydration to form the final adduct. This report describes the characterization and quantitative study of DNA adducts formed from lower chlorinated PCB-derived quinones. Quantitative study by HPLC/ESI-MS/MS and 3 2 P-postlabeling-HPLC gave the adduct levels in the range of 3-1200 adducts per 10 8 nucleotides. These results demonstrate that increasing chlorine substitution is associated with lower yields of DNA adduct. Although 3 2 P-postlabeling is more sensitive than HPLC/ESI-MS/MS for the quantitative analysis of DNA adducts, modification levels were severely underestimated by the 3 2 P-postlabeling assay as compared to the HPLC/ESI-MS/MS assay. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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