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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 and Objective: Experimental studies and epidemiological investigations indicate that uranium can have a wide range of effects on human health. However, its long-term effects, especially carcinogenicity, are still lacking a clear conclusion. In this paper, we simulate human inhalation of depleted uranium (DU) aerosol to study the malignant transformation of human bronchial epithelial cells induced by poorly soluble depleted uranium and lung cancer-related gene expression profiles. Methods: Immortalized human bronchial epithelial cells (BEAS-2B) of adenovirus-12 / SV40 were treated with poorly soluble depleted uranium oxide (dUO2). The doubling time, serum resistance, Formation rate and tumorigenicity of nude mice to identify the malignant transformation characteristics of the cells. The gene expression profiles of BEAS-2B cells transformed with depleted uranium were detected by using 213 lung cancer related genes. Results: The doubling time of BEAS-2B cells in the 5th generation after depleted uranium was significantly shortened, and the serum resistance was significantly enhanced. The 10th generation cells had anchorage independent growth characteristics (semi-solid agar colony formation) tumor. Dimethyl sulfoxide (DMSO) has a significant protective effect on the malignant transformation of BEAS-2B cells induced by depleted uranium. Chips from 213 lung cancer-related genes showed that more than 70 genes were significantly altered in transformed cells, of which more than 10 genes were significantly decreased. Conclusions: Depleted uranium is carcinogenic in vitro.