贫铀对人肾小管上皮细胞的恶性转化及苯乙酸、亚硒酸钠的抑制作用  

Transformation of human kidney cells to tumorigenic phenotype by depleted uranium and suppression by phenyl acetate and sodium selenite

作　　者：李蓉[1] 艾国平[1] 徐辉[1] 楼淑芬[1] 程天民[1] 粟永萍[1] 郑怀恩[1] 蒋建新[1] 黄跃生[1] 

机构地区：[1]第三军医大学军事预防医学院全军复合伤研究所,创伤烧伤复合伤国家重点实验室,重庆400038

出　　处：《第四军医大学学报》2004年第20期1897-1901,共5页Journal of the Fourth Military Medical University

基　　金：全军"十五"指令性课题 (0 1L0 61 )

摘　　要：目的 :探讨贫铀 (DU)是否会引起人肾小管上皮细胞 (HKC)向恶性表型转化 ,以及抑制物是否可有效地抑制这种恶性转化 .方法 :将HKC用可溶性DU溶液 (0 .0 6 3～ 0 .5 0 0g/L)作用 2 4h后 ,再与 1.0～ 2 .5 μmol/L的苯乙酸 (PA)或亚硒酸钠 (SS)孵育 1d～ 3mo,观察不同代龄细胞的集落形成率、生长曲线、刀豆蛋白 (ConA)凝集实验、半固体琼脂集落形成率及裸小鼠成瘤性 ;检测脆性组氨酸三联体 (FHIT)蛋白在转化细胞中的表达 .结果 :传约 2 0～ 30代后 ,HKC在半固体琼脂中形成集落 ,注入裸小鼠后成瘤 .部分转化细胞的FHIT蛋白表达也较正常HKC减弱 .PA ,SS可明显减少HKC在半固体琼脂集落形成率至 (0 .6± 0 .1)‰ ,裸小鼠也无皮下肿瘤形成 (0 /3) (P <0 .0 5 ) .结论 :DU可诱发HKC向恶性表型转化 ;用PA ,SS抑制这种恶性转化的效果相似 .AIM: To investigate whether depleted uranium (DU) could transform human kidney cells (HKC) to tumorigenic phenotype and whether anti-tumor inhibitor could be used as an effective measure to prevent carcinogenesis. METHODS: After 24 h exposure to soluble DU (0.063- 0.500 g/L), HKCs were incubated for 1 day to 3 months with or without 1.0-2.5 μmol/L phenyl acetate or sodium selenite. The colony form efficient (CFE), growth curve and ConA agglomeration test in cells were observed. Some experiments such as anchorage-independent growth, tumor formation in nude mice, production of fragile histidine triad (FHIT)tumor-suppressor protein in cells were conducted. RESULTS: From 20 to 30 passages, HKC induced by DU formed colonies in soft agar and produced tumor in athymic mice. Expression of FHIT protein in some cells decreased. Both phenyl acetate and sodium selenite reduced the frequency of colony formation in soft agar to (0.6±0.1)‰. No tumor was found in athymic mice (0/3) (P<0.05). CONCLUSION: HKCs treated with DU solution are transformed into tumorigenic phenotype. The transformation in vitro can be suppressed effectively by phenyl acetate and sodium selenite.

关 键 词：贫铀 恶性表型 苯乙酸 亚硒酸钠 

分 类 号：R818[医药卫生—放射医学]