AFLATOXIN B-1 REDUCES NA-P-I COTRANSPORT IN PROXIMAL RENAL EPITHELIUM- STUDIES IN OPOSSUM KIDNEY (OK) CELLS()

In vivo studies indicate that aflatoxin B-1 (AFB(1)) may affect the re nal regulation of inorganic phosphate (P-i), possibly by altering the renal response to parathyroid hormone (PTH). Therefore, the present st udy utilized opossum kidney (OK) cells, a mammalian renal epithelial c ell line, to determine whether AFB(1) exposure alters sodium-phosphate (Na+-P-i) co-transport and the hormonal modulation thereof. OK cells are an established renal cell line with many properties analagous to t he proximal renal epithelium, including receptors for PTH, insulin, an d high levels of Na+-P-i co-transport. PTH and insulin have been shown to decrease and increase Na+-P-i co-transport, respectively, in OK ce lls. In the present study, AFB(1)-treated cells responded to PTH; howe ver, AFB(1) exposure decreased Na+-P-i uptake such that additional dec reases in Na+-P-i uptake in response to PTH were minimal. In the prese nce of insulin, AFB(1)-treated cells were only able to increase Na+-P- i uptake to levels 30% below that of control cells. The net result was that the range of the proximal renal epithelium to adjust Na+-P-i co- transport in response to hormonal modulation was reduced by AFB(1) exp osure. Sodium-dependent L-alanine uptake was measured and was found no t to be affected by the highest concentration of AFB(1); thus, indicat ing that AFB(1) exposure may have specific effects on Na+-P-i uptake a nd does not generally inhibit Na+-dependent transport. These observati ons are evidence that AFB(1) exposure may alter key elements of renal function. Such effects raise concern that AFB(1) exposure may have bro ad physiological impact in addition to its known carcinogenic properti es.