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Tumor tissue was obtained from residents of regions in Bosnia, Croatia and Serbia where endemic nephropathy has been prevalent for over 50 years. Fifty\u2010nine <jats:italic>TP53<\/jats:italic> mutations were detected in 42 of the 97 tumors analyzed. Mutational spectra were dominated by A:T to T:A transversions with the mutated adenines located almost exclusively on the nontranscribed strand. This marked strand bias is attributed to selective processing of aristolactam\u2010dA adducts by transcription\u2010coupled nucleotide excision repair. Hotspots for A:T to T:A mutations include codons 131 and 179 and the 5\u2032\u2010AG acceptor splice site of intron 6. The unique <jats:italic>TP53<\/jats:italic> mutational signature for AA identified in this study can be used to explore the hypothesis that botanical products containing this human carcinogen and nephrotoxin are responsible, in part, for the high prevalence of UUC and chronic renal disease in countries where <jats:italic>Aristolochia<\/jats:italic> herbal remedies traditionally have been used for medicinal purposes.<\/jats:p>","DOI":"10.1002\/ijc.26077","type":"journal-article","created":{"date-parts":[[2011,3,16]],"date-time":"2011-03-16T18:49:20Z","timestamp":1300301360000},"page":"1532-1536","source":"Crossref","is-referenced-by-count":96,"title":["<i>TP<\/i>53 Mutational signature for aristolochic acid: an environmental carcinogen"],"prefix":"10.1002","volume":"129","author":[{"given":"Masaaki","family":"Moriya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Slade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Brdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvonimir","family":"Medverec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Tomic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojan","family":"Jelakovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sim","family":"Truong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur 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