Aristolochic acid (AA), a potent human carcinogen produced by Aristolochia plants, is associated with urothelial carcinomas of the upper urinary tract (UUC). Following metabolic activation, AA reacts with genomic DNA to form aristolactam(AL)-DNA adducts, which concentrate in the renal cortex, where they serve as a sensitive and specific biomarker of exposure, while giving rise in the urothelium to a unique mutational signature in the TP53 tumor suppressor gene. Using AL-DNA adducts and the TP53 mutation spectra as biomarkers, we conducted a molecular epidemiologic study of UUC in Taiwan, where the incidence of UUC is the highest of any country in the world. AL-DNA adducts were found in the renal cortex of 86% of patients with A:T to T:A mutations in TP53, FGFR3 or HRAS. We conclude that  ingestion of Aristolochia-based herbal remedies in Taiwan contributes significantly to the incidence of UUC, a finding with significant implications for global public health.

Molecular toxicology of aristolochic acid-associated urothelial carcinoma in Taiwan

244th National Meeting (2012)

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