Noninvasive measurement of aristolochic acid-DNA adducts in urine samples from aristolochic acid-treated rats by liquid chromatography coupled tandem mass spectrometry: Evidence for DNA repair by nucleotide-excision repair mechanisms
| Autor: | Wan Chan, Elvis M. K. Leung |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
DNA Repair Health Toxicology and Mutagenesis Aristolochic acid Urine Urinalysis Tandem mass spectrometry Sensitivity and Specificity Adduct Rats Sprague-Dawley DNA Adducts chemistry.chemical_compound Deoxyadenosine Limit of Detection Tandem Mass Spectrometry Genetics Animals Deoxyguanosine Molecular Biology Chromatography Rats chemistry Carcinogens Aristolochic Acids Quantitative analysis (chemistry) Chromatography Liquid Nucleotide excision repair |
| Zdroj: | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. :1-6 |
| ISSN: | 0027-5107 |
| DOI: | 10.1016/j.mrfmmm.2014.05.004 |
| Popis: | Nephrotoxic aristolochic acids (AAs) form covalently bonded DNA adducts upon metabolic activation. In this work, a non-invasive approach to detect AAs exposure by quantifying urinary excreted DNA-AA adducts is presented. The developed method entails solid-phase extraction (SPE) enrichment of the urine-excreted DNA-AAs adducts, addition of internal standard, and quantification by liquid chromatography coupled tandem mass spectrometric (LC–MS/MS) analysis. Quantitative analysis revealed 7-(deoxyadenosine- N 6 -yl)-aristolactam II and 7-(deoxyguanosine- N 2 -yl)-aristolactam I that were previously detected as major DNA-AA adducts in different organs of AA-dosed rats, were detected as the major urine excreted adducts. Lower levels of 7-(deoxyadenosine- N 6 -yl)-aristolactam I and 7-(deoxyguanosine- N 2 -yl)-aristolactam II were also detected in the collected urine samples. The identities of the detected urinary DNA-AA adducts were confirmed by comparing chromatographic retention time with synthetic standards, by high-accuracy MS, and MS/MS analyses. LC–MS/MS analysis of the urine samples collected from the AAs-dosed rats demonstrated a time-dependent decrease in the urinary adduct levels, indicating the urinary DNA-AA adduct levels were reflective of the tissue adduct levels. It is expected that the developed approach of detecting urinary DNA-AA adducts will facilitate further carcinogenesis investigations of AAs. |
| Databáze: | OpenAIRE |
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