Aristolochic Acid, used in herbal remedies, linked to urothelial cancers and neuropathic diseases

By Katherine Maiorisi

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Dr. Grollman of Stony Brook University was honored in 2011 with the Environmental Mutagen Society (EMS) award for his work on aristolochic acid (AA) and its relation to cancer and neuropathy [1]. Throughout the past fifty years studies have been done on the effect of environmental agents on neuropathy. Aristolochia poisoning was first proposed in 1969 by Ivi´c, but was disregarded, until in 2005, when Dr. Grollman revisited the hypothesis. Due approximately 100 reports of chronic renal disease that developed in Belgian woman who had used Chinese herbs as a dietary supplement sparked an interest in investigating the effects of AA on the kidneys and cancers. Also, in Taiwan had the highest recordings of upper urinary tract carcinomas in the world, and a third of the population used herbal remedies containing aristolocia. Dr. Grollman’s hypothesis for experimentation with AA was that “dietary ingestion of AA in conjunction with genetic sensitivity accounts for all epidemiologic, clinical, and pathophysiologic features of EN and UCC”. AA can cause a unique TP53 gene mutation in urothelial tumors. These mutations are evident markers of AA poisoning [1]. The study involved nineteen subjects who were directly exposed to AA whose tissue was exome sequenced. It was determined that AA is a primary contributor to urinary tract issues in Taiwan. The sample of people was based on a previous study conducted by Dr. Grollman with a population of 151 Taiwanese patients [2].

To conduct his research Dr. Grollman had to conduct background research on Chinese culture to determine when herbal remedies changed and when AA was used. This posed a challenge because of the language barrier between Chinese cultural literature and English translations of the text. It has been determined that there is no treatment for cancers or neuropathic diseases that were developed as a result of AA, once it is taken it cannot be removed from the body, it is the “most potent carcinogen”. The only effects AA has on the human body are urothelial cancers and neuropathic diseases; they do not cause medical issues for other organs or cells. Currently Dr. Grollman is working on developing the answers to how AA causes the mutations in the TP53 gene [3].

 

[1] Grollman, A. 2012. Aristolochic Acid Neuropathy: Harbinger of a Global Iatrogenic Disease. Environmental and Molecular Mutagenesis. 1-7.

[2] 2013. DNA Sequence Analysis Links a Human Carcinogen to a Specific Mutation. Stony Brook News.

[3] Grollman, Arthur. Telephone interview. 14 February 2014.

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