Quantum dot-induced epigenetic and genotoxic changes in human breast cancer cells
Quantum dot-induced epigenetic and genotoxic changes in human breast cancer cells
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DOI：
10.1007/s00109-007-0274-2
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发表时间：
2008-03-01
影响因子：
4.7
通讯作者：
Maysinger, Dusica
中科院分区：
文献类型：
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作者：
Choi, Angela O.;Brown, Shelley E.;Maysinger, Dusica
在我们的环境中发现的纳米技术产品和适用于医学的纳米技术产品的惊人阵列，激发了人们对研究其对遗传和表观遗传过程的长期影响的兴趣。我们在这里研究了人类乳腺癌细胞对碲化镉量子点（QD）的表观基因组和遗传毒性反应。QD处理诱导了全局低乙酰化，这意味着全局表观基因组应答。基因毒性应激的普遍应答者p53被QD激发激活，导致p53易位，随后上调下游靶点Puma和Noxa。p53抑制剂pifithrin-alpha部分阻止了细胞活力的相应降低，表明p53易位有助于QD诱导的细胞毒性。这些发现表明纳米颗粒诱导的细胞变化有三个层次：非基因组、基因组和表观遗传。表观遗传变化可能在初始信号被移除很久之后对基因表达编程产生长期影响，如果这些变化仍未被检测到，则可能导致生物系统中的长期不良影响。这些研究表明，除了遗传毒性效应，纳米粒子可能会导致更微妙的表观遗传变化，值得对环境纳米粒子和新的候选纳米材料进行彻底的检查，用于医疗应用。
The staggering array of nanotechnological products, found in our environment and those applicable in medicine, has stimulated a growing interest in examining their long-term impact on genetic and epigenetic processes. We examined here the epigenomic and genotoxic response to cadmium telluride quantum dots (QDs) in human breast carcinoma cells. QD treatment induced global hypoacetylation implying a global epigenomic response. The ubiquitous responder to genotoxic stress, p53, was activated by QD challenge resulting in translocation of p53, with subsequent upregulation of downstream targets Puma and Noxa. Consequential decrease in cell viability was in part prevented by the p53 inhibitor pifithrin-alpha, suggesting that p53 translocation contributes to QD-induced cytotoxicity. These findings suggest three levels of nanoparticle-induced cellular changes: non-genomic, genomic and epigenetic. Epigenetic changes may have long-term effects on gene expression programming long after the initial signal has been removed, and if these changes remain undetected, it could lead to long-term untoward effects in biological systems. These studies suggest that aside from genotoxic effects, nanoparticles could cause more subtle epigenetic changes which merit thorough examination of environmental nanoparticles and novel candidate nanomaterials for medical applications.