Cappelletti G, Incani C, Maci R
Dipartimento di Biologia, Università degli Studi di Milano, Italy.
Cell Biol Toxicol. 1994 Aug;10(4):255-63. doi: 10.1007/BF00756765.
The herbicide paraquat (PQ) induces the selective necrosis of type I and type II alveolar pneumocytes. We investigated the effect of PQ on human lung A549 cells to determine the possible role of cytoskeleton in lung cytotoxicity. At 80 mumol/L PQ, a concentration that did not affect cell viability, the organization of actin cytoskeleton network depended on incubation time with the herbicide. Microfilaments appeared less numerous in 30% of the cells treated for 1 h. After 24 h, all the treated cells displayed only short filaments in the periphery. The effect of PQ on actin cytoskeleton was irreversible. Moreover, no modification of microtubule network was observed in PQ-treated cells. Next, we studied the effect of PQ on Chang Liver, an epithelial cell line from human liver. These cells appeared less sensitive to the herbicide than A549, and no cytoskeletal alteration was observed. To verify whether actin filament modifications in A549 cells were related to intracellular alterations of ATP concentrations, nucleotide levels during incubation with PQ were determined. The intracellular levels of ATP were not different in control and treated cells. Our results indicate that PQ induces specifically an irreversible actin filament disorganization on A549 cells and that the observed effect is independent of intracellular concentration of ATP.
除草剂百草枯（PQ）可诱导I型和II型肺泡上皮细胞发生选择性坏死。我们研究了PQ对人肺A549细胞的影响，以确定细胞骨架在肺细胞毒性中可能发挥的作用。在80 μmol/L的PQ浓度下（该浓度不影响细胞活力），肌动蛋白细胞骨架网络的组织情况取决于与除草剂的孵育时间。在处理1小时的细胞中，30%的细胞内微丝数量减少。24小时后，所有处理过的细胞仅在周边显示出短丝。PQ对肌动蛋白细胞骨架的影响是不可逆的。此外，在经PQ处理的细胞中未观察到微管网络的改变。接下来，我们研究了PQ对人肝上皮细胞系Chang Liver的影响。这些细胞对除草剂的敏感性似乎低于A549细胞，且未观察到细胞骨架改变。为了验证A549细胞中肌动蛋白丝的改变是否与ATP浓度的细胞内变化有关，我们测定了与PQ孵育期间的核苷酸水平。对照细胞和处理细胞中的细胞内ATP水平没有差异。我们的结果表明，PQ可特异性地诱导A549细胞中肌动蛋白丝发生不可逆的解聚，且观察到的效应与细胞内ATP浓度无关。
