EFFECT ON DOME FORMATION AND UPTAKE OF OCHRATOXIN-A IN PROXIMAL TUBULE-DERIVED OPOSSUM KIDNEY-CELL MONOLAYERS

Ochratoxin A (OTA) is a mycotoxin produced by several different fungi, with the kidney as the main target. Many studies have suggested that the proximal tubule is an important intrarenal target. The purpose of this study was (i) to show that opossum kidney cells are a suitable model for studying proximal tubule toxicity by monitoring the effects on dome formation and (ii) to investigate how the mycotoxin enters proximal tubular cells. Dome formation of OK cells is affected by OTA in a biphasic manner: a decrease in the dome number (to 0% of control after 50 h) in the presence of high concentrations (10(-5) mol/l) and stimulation (to 166 % of control after 50 h) in the presence of low concentrations (10(-7) mol/l) of the mycotoxin. Furthermore, the uptake across the luminal membrane is mediated by at least three transport systems with high affinity: the L-phenylalanine carrier, the H+-driven dipeptide carrier and the organic anion carrier. For the uptake across the basolateral membrane, only the organic anion carrier could be identified, exerting a low affinity. These findings suggest that (i) filtered OTA is resorbed in the proximal tubule, thus lowering the final urinary excretion, and (ii) that OTA may be accumulated in proximal tubular cells.