کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2146314 | 1548332 | 2014 | 6 صفحه PDF | دانلود رایگان |

• We have developed a non-invasive approach to detect AAs exposure.
• DNA-AA adducts were detected in urine samples collected from AAs-dosed rats.
• DNA-AA adducts were repair by nucleotide-excision repair mechanisms.
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-N6-yl)-aristolactam II and 7-(deoxyguanosine-N2-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-N6-yl)-aristolactam I and 7-(deoxyguanosine-N2-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.
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volumes 766–767, August–September 2014, Pages 1–6