SELECTIVE EXPOSURE OF HUMAN PROXIMAL TUBULE CELLS TO GENTAMICIN PROVIDES EVIDENCE FOR A BASOLATERAL COMPONENT OF TOXICITY

The goal of the present study was to determine if cultured human proxi mal tubule (HPT) cells could provide evidence for a basolateral compon ent of gentamicin toxicity. Six isolates of HPT cells were grown on Mi llicell filters and exposed to gentamicin either apically, basolateral ly, or both apically and basolaterally. Toxicity was determined by the release of lactate dehydrogenase into the growth media. The results c learly demonstrated that basolateral exposure and combined apical and basolateral exposure to gentamicin resulted in significant levels of c ell toxicity. In contrast, apical exposure to gentamicin elicited only marginal toxicity. The transepithelial flux of gentamicin was shown t o be the same in either the apical to basolateral or the basolateral t o apical direction. A two-step mechanism of gentamicin toxicity is pro posed in order to integrate basolateral toxicity with known features o f aminoglycoside nephrotoxicity.