PDF(Sci-hub)
Abstract：
Cellular senescence is a stable cell cycle arrest induced by diverse triggers, including replicative exhaustion, DNA damaging agents, oncogene activation, oxidative stress, and chromatin disruption. With important roles in aging and tumor suppression, cellular senescence has been implicated also in tumor promotion. Here we show that certain multiwalled carbon nanotubes (MWCNTs), as fiber-like nanomaterials, can trigger cellular senescence in primary human mesothelial cells. Using in vitro approaches, we found manifestation of several markers of cellular senescence, especially after exposure to a long and straight MWCNT. These included inhibition of cell division, senescence-associated heterochromatin foci, senescence-associated distension of satellites, LMNB1 depletion, γH2A.X nuclear panstaining, and enlarged cells exhibiting senescence-associated β-galactosidase activity. Furthermore, genome-wide transcriptome analysis revealed many differentially expressed genes, among which were genes encoding for a senescence-associated secretory phenotype. Our results clearly demonstrate the potential of long and straight MWCNTs to induce premature cellular senescence. This finding may find relevance in risk assessment of workplace safety, and in evaluating MWCNT\'s use in medicine such as drug carrier, due to exposure effects that might prompt onset of age-related diseases, or even carcinogenesis.
摘要：
细胞衰老是由多种触发因素引起的稳定的细胞周期停滞，包括复制性耗尽，DNA损伤剂,癌基因激活，氧化应激，和染色质破坏。在衰老和肿瘤抑制中具有重要作用，细胞衰老也与肿瘤的促进有关。在这里，我们展示了某些多壁碳纳米管(MWCNT)，作为纤维状纳米材料，可以在原代人间充质细胞中引发细胞衰老。使用体外方法，我们发现了几种细胞衰老标记的表现，特别是在暴露于长而直的MWCNT之后。这些包括抑制细胞分裂，衰老相关异染色质灶，与衰老相关的卫星扩张，LMNB1耗尽，γH2A。X核泛染，和显示衰老相关β-半乳糖苷酶活性的扩大细胞。此外，全基因组转录组分析揭示了许多差异表达的基因，其中有编码衰老相关分泌表型的基因。我们的结果清楚地证明了长而直的MWCNT诱导细胞过早衰老的潜力。这一发现可能会在工作场所安全的风险评估中找到相关性，在评估MWCNT在药物载体等药物中的应用时，由于暴露效应可能会促使年龄相关疾病的发作，甚至致癌作用。
