Balkan endemic nephropathy (BEN) and aristolochic acid nephropathy (AAN) originally described in late 1950’s and early 1990’s respectively, have stirred a lot of debate and research aimed at identifying the causative agent(s). Exposure of AAN patients to aristolochic acids (AAs) that belong to the family of carcinogenic, mutagenic and nephrotoxic compounds was substantiated by the idenfication of AA– DNA adducts. The unique renal histopathology and the remarkably high incidence of upper urothelial cancer (UUC) of AAN, with its striking similarity to BEN, have led to the hypothesis of a common etiological agent for both diseases. The TP53 mutation spectrum in AA-induced UUC displays some unique features, including the predominance of A:T → T:A transversions. It was proposed that in BEN chronic human exposure to a toxic component of Aristolochia might occur through ingestion of bread prepared from flour derived from contaminated wheat grain, whereas AAN resulted from the acute accidental poisoning. In light of the widespread use of Aristolochia herbal remedies in traditional medicine of many countries, and recently published data that some crops can take up AAs from the culture media, we have raised the question: Could AAs, originating from decayed Aristolochia clematitis plant and fruit in the soil, which were later taken up and transported into edible food crops to cause BEN and/or AAN, be responsible for a previously and currently unrecognized renal disease and UUC on the worldwide scale? Using the highly sensitive and selective high- performance liquid chromatography coupled with fluorescence detection method, we identified and quantitated in this study for the first time AAs in corn, wheat grain, and soil samples collected from the endemic village Kutles in Serbia. Our results provide the first direct evidence that food crops and soil in the Balkans are contaminated with AAs. To the best of our knowledge, this is the first report demonstrating the detection of AAs in environmental and food samples. It is possible that the presence of AAs in edible parts of crops originating from the AA-contaminated soil could be one of the major pathways by which humans become exposed to AAs all over the world.

Identification and quantitation of naturally-occuring carcinogens, aristolochic acids, in raw ag commodities and soil: Identification and estimation of novel exposure pathway (2017 JAFC Award address)

254th National Meeting (2017)

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