title: Genotoxicity of mesoporous silica nanoparticles in human embryonic kidney 293 cells.
abstract: Mesoporous silica nanoparticles (MSNs) have been widely evaluated for their potential use as carriers for cancer diagnosis and therapy. Understanding the toxicity of MSNs is crucial to their biomedical applications. Although several groups have reported the cytotoxicity of MSNs, the genotoxicity (inducing genetic aberrations) of MSNs in normal human cells has not been extensively investigated. Gene amplification and mutation may initiate and promote carcinogenesis, and changes in mRNA expression can affect normal human physical functions. In this study, human embryonic kidney 293 (HEK293) cells were treated overnight with MSNs at a concentration of 120 µg/mL. The cells were assayed with fluorescent in situ hybridization to check for chromosome changes and gene amplification. Mutations in the epidermal growth factor receptor 1 (EGFR1) and KRAS genes were checked with DNA sequencing. The effects of MSNs on mRNA expression were investigated with an Agilent human mRNA microarray. No chromosomal alterations or gene mutations in EGFR or KRAS were observed in the control HEK293 cells or HEK293 cells exposed to MSNs. The microarray analysis showed that MSNs significantly altered gene expression. The expression of 579 genes was upregulated and that of 1263 genes was downregulated in HEK293 cells treated with MSNs compared with the control HEK293 cells. Our findings suggest that exposure to MSNs is genotoxic to normal human cells, leading to changes in the expression of some genes. This genotoxicity may cause cellular dysfunction and certain benign diseases. We have not shown that MSN exposure induces serious genotoxicity involving carcinogenesis.
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Quanan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Hanfeng
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Shengqin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Southeast University, Nanjing, 210009, Jiangsu, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, Jiangsu, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wang
mesh_terms: D004249:DNA Damage / Q000187:drug effects*; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D053758:Nanoparticles / Q000633:toxicity*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: C117307:KRAS protein, human; D009153:Mutagens; D012822:Silicon Dioxide; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: HEK293 cell; MSN; genotoxicity; human embryonic kidney cell line