贫铀对人肾小管上皮细胞的毒性作用

Acute toxic effects of depleted uranium and/or phenyl acetate and sodium selenite on human kidney epithelial cells

目的 阐明贫铀 (depleteduranium ,DU)对人肾小管上皮细胞 (humankidneycell,HKC)的急性毒性作用及损伤部位 ,为救治提供依据。方法 将 0 0 63～ 0 5 0 0mg ml的DU溶液作用于HKC ,研究细胞超微结构、存活率的变化 ,多种酶含量的改变及HGPRT基因突变的频率。结果 0 0 63～ 0 5 0 0mg ml浓度的DU可引起HKC细胞结构改变 ,存活率显著下降 ;溶酶体酶NAG含量随DU浓度的增加而增加 ;其他酶含量也发生变化 ;HGPRT基因突变的发生率显著高于正常对照组 ,并呈二项式相关关系。加入苯乙酸、亚硒酸钠使上述指标变化不大。结论 DU可引起细胞活力降低 ,损伤细胞膜、线粒体、溶酶体等 ,使细胞抗氧化能力下降 ;HGPRT基因突变率与DU浓度之间呈相关关系 ;加入恶性转化的抑制剂亚硒酸钠和苯乙酸 。

Objective To investigate the acute toxic effect of depleted uranium (DU) on human kidney cells (HKCs). Methods We used a model system of in vitro HKCs exposed to DU (0 063-0 500 mg/ml) and phenyl acetate or sodium selenite for 24 h. Morphological changes of cellular ultrastructure, surviving fractions of cells, contents of multiple enzymes, and gene mutation frequency of hypoxanthine guanine phosphoribosyltransferase (HGPRT) were studied. Results A certain concentration of DU could induce the changes of cellular structure of HKCs and reduce the survival rate of cells in a dose dependent manner. Concentrations of NAG, GCR, and LDH increased signifi cantly , but those of SOD and GSH PX reduced in a dose dependent manner. Mutation frequency of HGPRT induced by DU was higher than that in the control group and that of the spontaneous mutation. Conclusion DU can induce reduced cellular vitality, injured cell membrane, mitochondria, and lysosome, resulting in declined antioxidation capability of cells. The mutation frequency of HGPRT increases in a dose dependent manner. Treatment of HKCs with phenyl acetate and sodium selenite after exposure to DU does not significantly increase the toxic effect of DU.