Characterization and Quantitative Analysis of DNA Adducts Formed from Lower Chlorinated PCB-Derived Quinones

Shouxun Zhao, Amarjit Narang, Xinxin Ding, George Eadon

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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 32P-postlabeling-HPLC gave the adduct levels in the range of 3-1200 adducts per 108 nucleotides. These results demonstrate that increasing chlorine substitution is associated with lower yields of DNA adduct. Although 32P-postlabeling is more sensitive than HPLC/ESI-MS/MS for the quantitative analysis of DNA adducts, modification levels were severely underestimated by the 32P-postlabeling assay as compared to the HPLC/ESI-MS/MS assay.

Original languageEnglish (US)
Pages (from-to)502-511
Number of pages10
JournalChemical Research in Toxicology
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

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