摘要
背景与目的:实验研究和流行病学调查结果表明,铀可广泛地影响人体健康,但其远期效应,特别是致癌性,还缺乏明确的结论。本文模拟人吸入贫铀(depleteduranium,DU)气溶胶的情形,研究难溶性贫铀诱发人支气管上皮细胞恶性转化及肺癌相关基因表达谱。方法:用难溶性贫铀氧化物(dUO2)作用腺病毒-12/SV40病毒永生化的人支气管上皮细胞(BEAS-2B),通过观察不同代龄细胞的倍增时间、血清抗性、半固体琼脂克隆形成率及裸鼠成瘤性,鉴定细胞的恶性转化特性;用213个肺癌相关基因的芯片对贫铀诱发的转化BEAS-2B细胞的基因表达谱进行检测。结果:贫铀作用后的第5代BEAS-2B细胞倍增时间明显缩短,血清抗性显著增强;第10代细胞具有锚着独立性生长特性(半固体琼脂克隆形成);第15代裸鼠体内成瘤。二甲亚砜(DMSO)对贫铀诱发的BEAS-2B细胞恶性转化有明显保护效果。213个肺癌相关基因的芯片检测结果表明,转化细胞中有70多个基因的表达水平发生明显改变,其中10余个基因表达水平明显下降。结论:贫铀在体外具有致癌性。
Background &Objective:It is clear from works already reported that depleted uranium(DU)affect human health.However,the late effe ct,especially the carcinogenesis,was not clearly understood.This stu dy was designed to investigate the malignant transformation of human bronchial epithelial cell induced by insoluble DU and l ung cancer related gene expression pattern,through im itating the condition that human absorbs depleted uranium aerosol.Methods:Adenovirus-12/SV40virus immortalized human bronchial epithelial cells(BEAS-2B)were reacted with insoluble DU oxide(dUO2);the characteristics of malignant t ransformation of cells were identif ied through observing the multiplic ation time of different generation cells,serum r esistance,colony formation rate of semi-solid agar,and tumorigenesis in nude mice.Gene expression pattern of transferred B EAS-2B cell induced by DU was determi ned using 213lung cancer related gen e arrays.Results:The multiplication time of BEAS-2B c ell treated with DU was obviously dec reased and the serum resistance was significantly increased in 5th generation;the anchorage independent g rowth(semi-solid agar colony formation)was appeared in 10th generation cell.The 15th gen eration cell formed tumor in nude mic e.DMSO showed overt protection effe ct on malignant transformation of BEAS-2B cell.The analyzing results of 213l ung cancer related gene arrays showe d that the expression level changed in more than 70genes of transferred cells,including the overt decrease of level of gene expression in more than 10genes.Conclusion:DU has carcinogenesis in vitro.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2002年第9期944-948,共5页
Chinese Journal of Cancer
基金
全军"十五"指令课题(NO.01L061)
关键词
贫铀
人支气管上皮细胞
细胞恶性转化
基因表达
Depleted uranium
Human bronchial e pithelial cell(BEAS-2B)
Malignant transformation
Gene ex pression
