Variation in gentamicin-induced death among independent cultures of proximal tubule cells

This study determined the sensitivity of 12 independent isolates of cultured human proximal tubule (HPT) cells to gentamicin. The TD50 (dose [microgram per ml]) for each isolate was determined by linear regression analysis of cells exposed to a wide concentration range of gentamicin over a 16-day period of exposure. The results of this determination clearly showed that within a series of HPT cell cultures there was significant diversity in sensitivity to gentamicin. Three groups of toxic response were delineated. A single isolate, isolate I, was extremely resistant to gentamicin toxicity and was the sole member of group 1. The majority (9 of 12) of the isolates demonstrated intermediate sensitivity to gentamicin and were classified as group 2. Group 3 included two isolates that were very sensitive to gentamicin, with relatively low doses producing cell death. These results provide initial evidence that a portion of the variability seen in nephrotoxicity among patients receiving the aminoglycoside antibiotics might be mediated by factors intrinsic to each individual's proximal tubule cells.