%0 Journal Article
%A Schmeiser, Heinz
%A Nortier, Jöelle L
%A Singh, Rajinder
%A Gamboa da Costa, Gonçalo
%A Sennesael, Jacques
%A Cassuto-Viguier, Elisabeth
%A Ambrosetti, Damien
%A Rorive, Sandrine
%A Pozdzik, Agnieszka
%A Phillips, David H
%A Stiborova, Marie
%A Arlt, Volker M
%T Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy.
%J International journal of cancer
%V 135
%N 2
%@ 0020-7136
%C Bognor Regis
%I Wiley-Liss
%M DKFZ-2017-04287
%P 502-507
%D 2014
%X Aristolochic acid (AA) causes aristolochic acid nephropathy (AAN), first described in women in Belgium accidently prescribed Aristolochia fangchi in a slimming treatment, and also Balkan endemic nephropathy (BEN), through probable dietary contamination with Aristolochia clematitis seeds. Both nephropathies have a high risk of urothelial cancer, with AA being the causative agent. In tissues of AAN and BEN patients, a distinct DNA adduct, 7-(deoxyadenosin-N6-yl)-aristolactam I (dA-AAI), has been detected. DNA adducts can be removed through DNA repair, they can result in mutations through erroneous DNA replication or they can cause cell death. The dA-AAI adduct induces AT to TA transversions in the tumor-suppressor TP53 gene in experimental systems, matching TP53 mutations observed in urothelial tumors from AAN cancer cases. Using thin-layer chromatography 32P-postlabeling and mass spectrometric analysis we report the detection of dA-AAI in renal DNA from 11 Belgian AAN patients over 20 years after exposure to AA had ceased. Our results showed that dA-AAI is an established biomarker of AA exposure, and that this biomarker can be demonstrated to be persistent decades after a distinct AA exposure. Further, the persistence of dA-AAI adducts appears to be a critical determinant for the AA mutational fingerprint frequently found in oncogenes and tumor suppressor genes recently identified by whole genome sequencing of AA-associated urothelial tumors. The potential for exposure to AA worldwide is high; the unprecedented long-term persistence of dA-AAI provides a useful long-term biomarker of exposure and attests to the role of AA in human urothelial malignancy.
%K Aristolochic Acids (NLM Chemicals)
%K Biomarkers (NLM Chemicals)
%K DNA Adducts (NLM Chemicals)
%K Mutagens (NLM Chemicals)
%K aristolochic acid I (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:24921086
%U https://inrepo02.dkfz.de/record/128270