Uranium is known as a nephrotoxicant that exert most of its toxicity on proximal tubule epithelial cells. Although renal damages induced by uranium acute intoxication have been largely studied in vivo, few in vitro data are available concerning the mechanisms implicated in its cytotoxicity.
The aim of this study was to characterize cell morphological changes consecutive to uranium acute exposure and to confirm that uranium cytotoxicity was correlated with its cellular intake. Phase contrast microscopic observation of NRK-52E rat kidney proximal tubule epithelial cells exposed to uranium and cadmium, the latter being considered as the reference nephrotoxicant, revealed very different morphological changes even if cellular repartition of these toxics, analyzed by nuclear microprobe imaging, is quite similar. Transmission and scanning electron microscopy images are reported, allowing a first step towards the comprehension of mechanisms of uranium intake and cell effects.
Control cells, observed in phase contrast microscopy at 100% confluency, are polyhedral and exhibit a compact cobblestone appearance (figure 1A) as previously described. Uranium toxicity appeared after 15 h uranyl-bicarbonate exposure. From this time, some of the cells appeared to have exploded, whereas others just nearby appeared to be insensitive to uranium exposure (figure 1B). The fields containing exploded cells expanded continuously with exposure time. The whole monolayer was reduced to fragments after 24 h exposure. These fragments remained attached to the semi-permeable culture membrane. In the case of cadmium exposure, the links between the cells rapidly and almost simultaneously broke (figure 1C); cells then detached from the culture membrane.