In the early nineties, about 100 young women who were dieting in the same clinic developed rapidly progressive renal failure within a few months, further complicated by the occurrence of urothelial carcinoma of the upper urinary tract. They ingested pills contaminated with Aristolochia fangchi that inadvertently replaced Stephania tetrandra. DNA adducts derived from aristolochic acid have been identified in tissue fragments from these patients. This AA-associated nephropathy, both in its clinical presentation, the associated tumour risk, and the histopathological appearance, is similar to the Balkan endemic nephropathy, a disease that has been known since the end of the 1950s, with no clear identification of the causative agent. The involvement of aristolochic acid in Balkan endemic nephropathy has been proved by the presence of DNA adducts formed by aristolochic acid in renal cortex fragments, indicating exposure to Aristolochia clematis, a plant contaminating wheat crops. In this population, genetic analysis of urothelial tumours reveals a high frequency of A>T transverse mutation. The presence of this mutation, considered as the mutational signature of aristolochic acid, had never been explored in Belgian patients. Analyzing the frozen ureteric fragments of 5 patients who had been dieting in the early 90s, we not only demonstrated the mutational signature of aristolochic acid but also the poly-or multiclonal character of tumour cells. In studies on mutational analyzes of tumour urothelial cells in patients with Balkan endemic nephropathy and in the Taiwanese population, areas of interest with more than 10% immunohistochemically labeled cells with p53 were analyzed. We extended our study to immunohistochemically negative areas for p53. These correspond to foci of urothelial dysplasia and frequently involve transverse mutations of A> T, which is an early phenomenon in urothelial carcinogenesis in patients with aristolochic acid nephropathy. ; (MED - Sciences médicales) -- UCL, 2018