Genotoxicity and molecular response of silver nanoparticle (NP)-based hydrogel

• Main Authors: Xu Liming, Li Xuefei, Takemura Taro, Hanagata Nobutaka, Wu Gang, Chou Laisheng
• Format: Article
• Language: English
• Published: BMC 2012-05-01
• Series: Journal of Nanobiotechnology
• Subjects: Silver nanoparticle-based hydrogel (silver-NP-hydrogel); Genotoxicity; Global gene expression; DNA damage; Apoptosis and mitosis pathway; JAK-STAT signal transduction pathway
• Online Access: http://www.jnanobiotechnology.com/content/10/1/16

<p>Abstract</p> <p>Background</p> <p>Since silver-nanoparticles (NPs) possess an antibacterial activity, they were commonly used in medical products and devices, food storage materials, cosmetics, various health care products, and industrial products. Various silver-NP based medical devices are available for clinical uses, such as silver-NP based dressing and silver-NP based hydrogel (silver-NP-hydrogel) for medical applications. Although the previous data have suggested silver-NPs induced toxicity in vivo and in vitro, there is lack information about the mechanisms of biological response and potential toxicity of silver-NP-hydrogel.</p> <p>Methods</p> <p>In this study, the genotoxicity of silver-NP-hydrogel was assayed using cytokinesis-block micronucleus (CBMN). The molecular response was studied using DNA microarray and GO pathway analysis.</p> <p>Results and discussion</p> <p>The results of global gene expression analysis in HeLa cells showed that thousands of genes were up- or down-regulated at 48 h of silver-NP-hydrogel exposure. Further GO pathway analysis suggested that fourteen theoretical activating signaling pathways were attributed to up-regulated genes; and three signal pathways were attributed to down-regulated genes. It was discussed that the cells protect themselves against silver NP-mediated toxicity through up-regulating metallothionein genes and anti-oxidative stress genes. The changes in DNA damage, apoptosis and mitosis pathway were closely related to silver-NP-induced cytotoxicity and chromosome damage. The down-regulation of CDC14A via mitosis pathway might play a role in potential genotoxicity induced by silver-NPs.</p> <p>Conclusions</p> <p>The silver-NP-hydrogel induced micronuclei formation in cellular level and broad spectrum molecular responses in gene expression level. The results of signal pathway analysis suggested that the balances between anti-ROS response and DNA damage, chromosome instability, mitosis inhibition might play important roles in silver-NP induced toxicity. The inflammatory factors were likely involved in silver-NP-hydrogel complex-induced toxic effects via JAK-STAT signal transduction pathway and immune response pathway. These biological responses eventually decide the future of the cells, survival or apoptosis.</p>