Okuda M, Tsuda K, Masaki K, Hashimoto Y, Inui K
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Toxicol Lett. 1999 Jun 1;106(2-3):229-35. doi: 10.1016/s0378-4274(99)00071-5.
Cytotoxicity of cisplatin was evaluated after apical and/or basolateral treatment of LLC-PK1 cell monolayers grown on porous membrane filters with 300 microM cisplatin. When LLC-PK1 cells were exposed from basolateral side for 0.5-4 h, lactate dehydrogenase (LDH) release into culture medium was markedly stimulated. However, apical treatment of the cells with cisplatin for 0.5 h did not stimulate LDH release. gamma-Glutamyltransferase activity and amount of protein in the cell homogenate were markedly decreased by basolateral treatment with cisplatin. However, in the apical treatment with cisplatin, these changes were relatively small, suggesting that degrees of the toxicities were different between basolateral and apical treatment with cisplatin. Cellular platinum level after basolateral treatment with cisplatin was higher compared to that following apical treatment. Furthermore, both accumulation and toxicity of cisplatin in LLC-PK1 cells were decreased by treatment with cisplatin at 4 degrees C. These results suggested that there were specific mechanisms mediating cisplatin uptake at the basolateral membranes of LLC-PK1 cells.
在用300微摩尔顺铂对生长在多孔膜滤器上的LLC - PK1细胞单层进行顶端和/或基底外侧处理后，评估了顺铂的细胞毒性。当LLC - PK1细胞从基底外侧暴露0.5 - 4小时时，乳酸脱氢酶（LDH）释放到培养基中的量显著增加。然而，用顺铂对细胞进行顶端处理0.5小时并未刺激LDH释放。通过顺铂基底外侧处理，细胞匀浆中的γ - 谷氨酰转移酶活性和蛋白量显著降低。然而，在用顺铂进行顶端处理时，这些变化相对较小，这表明顺铂基底外侧处理和顶端处理的毒性程度不同。与顶端处理相比，顺铂基底外侧处理后的细胞铂含量更高。此外，在4℃下用顺铂处理可降低LLC - PK1细胞中顺铂的积累和毒性。这些结果表明，在LLC - PK1细胞的基底外侧膜上存在介导顺铂摄取的特定机制。
