title: Variation in presentation and presence of DNA adducts and p53 mutations in patients with endemic nephropathy--an environmental form of the aristolochic acid nephropathy.
abstract: BACKGROUND
  Endemic nephropathy (EN) and associated urothelial cell cancers (UUC) are an environmental form of aristolochic acid nephropathy where the most probable rout of ingestion of aristolochic acid (AA) was made by bread contaminated with AA, leading to chronic dietary intoxication. Clinical courses of three members of the same family, similarly exposed to toxin, who exhibited different clinical courses of the disease are presented.
  
  
  METHODS
  Questionnaires on AA exposure were taken. Tissue samples were obtained during therapeutic nephrouretectomies. Histopathology, immunohistochemical detection of p53, p53 mutation screening in tumor DNA and analysis on the presence of aristolactam (AL)-DNA adducts were performed.
  
  
  RESULTS
  Case 1 had UUC with typical EN histopathological signs, whereas Case 2 had bilateral UUCs with typical EN histopathological signs. In contrast, the patient in Case 3 initially showed renal insufficiency, complicated afterwards by right UUC, and later on by left UUC with histopathological end-stage chronic changes but without typical EN changes. AA-DNA adducts and specific p53 mutational spectra (A:T→ T:A transversion) were found in tissues of cases 1 and 2.
  
  
  CONCLUSIONS
  Diverse clinical courses seem to be related not to differences in exposure but to differences in metabolic activation or detoxification of AA and/or DNA repair resulting from different genetic polymorphisms.
authors: School of Medicine, University of Zagreb, Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia.
authors: Sandra
authors: S
authors: Karanović
authors: Ivana Vuković
authors: IV
authors: Lela
authors: Bojan
authors: B
authors: Jelaković
authors: Kathleen G
authors: KG
authors: Dickman
authors: Anamarija Kovač
authors: AK
authors: Peić
authors: Damir
authors: D
authors: Dittrich
authors: Matej
authors: M
authors: Knežević
authors: Vesna
authors: V
authors: Matijević
authors: Andrea S
authors: AS
authors: Fernandes
authors: Frederick
authors: F
authors: Miller
mesh_terms: D034341:Aristolochic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D001449:Balkan Nephropathy / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics*; D018736:DNA Adducts / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
chemical_list: D034341:Aristolochic Acids; D018736:DNA Adducts; C000228:aristolochic acid I