Acquired resistance to rechallenge injury with uranyl acetate in LLC-PK1 cells

This study was conducted to determine whether cultured renal cells exposed to previous uranium injury would be resistant to subsequent insult, and if so, the mechanisms for this resistance. The addition of a toxic dose of uranyl acetate (UA) (1 X 10(-3) mol/L) for 48 hours to the culture medium significantly enhanced the release of lactate dehydrogenase (LDH) from LLC-PK1 cells, expressed as LDH activity in the medium corrected by protein content of the cells, compared with control conditions (31.5 +/- 3.6 vs 5.5 +/- 0.6 Wroblewski unit/microg protein, p < 0.01). Pretreatment with a toxic dose of UA (1 x 10(-3) mol/L for 24 hours) or heat stress (42 degrees C for 30 minutes) significantly lessened the extent of increase in LDH after exposure to toxic doses of UA for 48 hours (15.2 +/- 1.4 and 7.6 +/- 0.6 Wroblewski unit/microg protein, respectively). Pretreatment with a nontoxic dose of UA (3 x 10(-4) mol/L for 24 hours) had no effect on the release of LDH after a toxic dose of UA treatment (38.6 +/- 7.0 Wroblewski unit/microg protein). Quercetin (100 microm ) and staurosporine (0.1 microg/ml), both known to inhibit the development of thermotolerance, hindered acquisition of the resistance to rechallenge with UA (42.5 +/- 1.1 and 38.9 +/- 1.8 Wroblewski unit/microg protein, respectively). Quercetin did not modify the UA-induced increase in the release of LDH in cells not pretreated with UA or heat stress. It follows from these findings that LLC-PK1 cells previously exposed to a toxic dose of UA are resistant to rechallenged insult and that mechanisms similar to those for thermotolerance might contribute to this acquired resistances.