摘要
目的 探讨顺铂对猴和大鼠肾小管上皮细胞的毒性及半胱氨酸和GSH合成抑制剂BSO对其影响。方法 从猴和大鼠的肾脏分离培养的肾小管上皮细胞接种于 96孔培养板 ,培养 2 4h后加入一系列浓度的顺铂 ,或在加入顺铂前 16和 4h ,分别加入GSH合成抑制剂BSO和GSH的前体物半胱氨酸 ,继续培养 ,分别在 8、2 4和 48h 3个时间点用MTT方法检测细胞存活率。结果 顺铂对猴和大鼠肾小管上皮细胞有明显的毒性 ,在不同的时间点有各自的剂量 反应关系 ,顺铂对大鼠肾小管上皮细胞在 8、2 4和 48h 3个时间点半数抑制浓度 (IC50 )分别为 110 5 12、5 13 2 5和 71 2 4μmol L;BSO能使 3组IC50 均降低 ,分别为 66 0 0、2 1 43和 7 2 3 μmol L ,而半胱氨酸则使 3组IC50 均升高 ,均大于 5 0 0 0 μmol L ;顺铂对猴肾小管上皮细胞在 3个时间点IC50 分别为 3 0 2 6 0 0、12 3 8 3 5和 664 44 μmol L ;BSO使 3组IC50 分别降为480 10、10 8 61和 3 1 43 μmol L ,而半胱氨酸则可使 3组IC50 均大于 5 0 0 0 μmol L。 结论 顺铂对猴和大鼠肾小管上皮细胞均具有明显毒性作用 ,对猴的毒性低于大鼠 ;BSO可增强顺铂的细胞毒性 ,对大鼠的影响大于猴 ,而半胱氨酸对两种细胞的保护作用无显著性差异 ,提示细胞内GSH对顺铂所致肾小管上?
Objective To investigate the effects of L\|cysteine and DL\|buthionine\|(S,R)\|sulfoximine (BSO) on Cisplatin induced toxicity to renal tubular epithelial cells isolated from monkeys and rats.Methods Renal tubular epithelial cells were isolated from monkeys and rats and then inoculated into 96 well plates, after 24 hours' preincubation, a series of concentration of Cisplatin, in the presence and absence of L\|cysteine, precursor of GSH synthesis, or BSO, inhibitor of GSH synthesis, were added and coincubated, MTT assays were performed to test cell viability at 8,24 or 48 hours after coincubation. Results Cisplatin has time and concentration\|dependent cytotoxicity. The concentrations of Cisplatin that inhibited 50% cell growth (IC 50 ) of rat renal tubular epithelial cells at 8,24 and 48 hours were \{1 105 12\} μmol/L,513 25 μmol/L and 71 24 μmol/L,respectively, and IC 50 of Cisplatin to monkey renal tubular epithelial cells was \{3 026 00\} μmol/L,\{1 238 35\} μmol/L and 664 44 μmol/L,respectively; BSO made IC 50 of Cisplatin to rat renal cells lower down to 66 00 μmol/L,21 43 μmol/L and 7 23 μmol/L,respectively, and IC 50 of Cisplatin to monkey renal cells was 480 10 μmol/L,108 61 μmol/L and 31 43 μmol/L, respectively; while L\|cysteine made IC 50 of Cisplatin increase up to more than 5 000 μmol/L. Conclusion Cisplatin is dramatically toxic to renal tubular epithelial cells from monkeys and rats, but rat cells are more sensitive to cisplatin than monkey cells; BSO can enhance Cisplatin\|induced cytotoxicity, while L\|cysteine can protect Cisplatin\|induced cytotoxicity. It is possible that GSH can protect Cisplatin\|induced toxicity to renal tubular epithelial cells with species\|dependent difference.
出处
《卫生毒理学杂志》
CSCD
北大核心
2003年第1期24-27,共4页
Journal of Health Toxicology
