title: Pre-cancerous changes in urothelial endocytic vesicle leakage, fatty acid composition, and As and associated element concentrations after arsenic exposure.
abstract: The urothelium covering the luminal surface of the urinary bladder has developed an efficient permeability barrier that protects it against the back-flow of toxins eliminated in the urine. The subapical endocytic vesicles containing the urinary bladder fluid phase are formed during the micturition cycle by endocytosis processes of the superficial cells. In normal conditions, the permeability barrier of the endocytic vesicles blocks the passage of the fluid phase to the cellular cytoplasm and the fluid is recycled to the bladder lumen. The aim of this work was to investigate the alteration of the endocytic vesicle membrane permeability barrier to toxins such as iAs (inorganic arsenic) administered in drinking water. By using an induced endocytosis model and the fluorescence requenching technique, it is shown that the exposure of rats to ingestion of water containing iAs not only induced pre-cancerous morphological changes, but allowed the differential leakage of an endocytosed fluorescent marker, HPTS, and its quencher, DPX, (hydroxypyrene-1,3,6-trisulfonic acid and p-xylene-bis-pyridinium bromide, respectively) out of the vesicular lumen. The leakage of the cationic DPX was almost complete, while the release of the anionic HPTS molecule was partial and higher in arsenic-treated-rats than in controls. Such membrane alteration would allow the toxins to elude the permeability barrier and to leak out of the endocytic vesicles, thus establishing a "bypass" to the permeability barrier. The retention of As in the urinary bladder, assessed by synchrotron radiation X-ray fluorescence spectrometry (SR-μXRF), was lower than the kidney accumulation of arsenic previously observed by our group and was accompanied by altered concentrations of K, Ca, Fe, Cu and Zn, all ions related to cellular metabolism. The results support the hypothesis that low amounts of endocytosed As can accumulate in the interior of the urothelial superficial cells and initiate the cytotoxic effects reflected in the morphological alterations observed.
authors: Primera Cátedra de Biología Celular, H. y E., Instituto de Biología Celular-Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
authors: E J
authors: EJ
authors: Grasso
authors: G A
authors: GA
authors: Bongiovanni
authors: R D
authors: RD
authors: Pérez
authors: R O
authors: RO
authors: Calderón
mesh_terms: D000818:Animals; D001151:Arsenic / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D005227:Fatty Acids; D001151:Arsenic