title: Evaluating the toxicity of silver nanoparticles by detecting phosphorylation of histone H3 in combination with flow cytometry side-scattered light.
abstract: Post-translational modification of histones is linked to a variety of biological processes and disease states. This paper focuses on phosphorylation of histone H3 at serine 10 (p-H3S10), induced by silver nanoparticles (AgNPs) and discusses the usefulness of p-H3S10 as a marker to evaluate the toxicity of AgNPs. Cultured human cells showed remarkable p-H3S10 immediately after treatment with AgNPs but not with Ag microparticles. p-H3S10 lasts up to 24 h and strongly depends upon the cellular uptake of AgNPs. Removal of Ag ions suppressed p-H3S10, while adding an excess of Ag ions augmented p-H3S10. We expected that p-H3S10 requires two events: cellular uptake of AgNPs and continuous release of Ag ions from intracellular AgNPs. AgNPs enhanced the expression of the proto-oncogene c-jun, and p-H3S10 increased in the promoter sites of the gene, indicating that p-H3S10 might indicate a biological reaction related to carcinogenesis. We previously showed that side-scattered light from flow cytometry could be used to measure the uptake potential of nanoparticles [ Suzuki , H. ; Toyooka , T. ; Ibuki , Y. Simple and easy method to evaluate uptake potential of nanoparticles in mammalian cells using a flow cytometric light scatter analysis . Environ. Sci. Technol. 2007 , 41 ( 8 ), 3018 - 3024 ]. Our current findings suggest that p-H3S10 can be used to evaluate the toxicity of AgNPs and Ag ion release in combination with detection of side-scattered light from flow cytometry.
authors: Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Suruga, Shizuoka, Shizuoka 422-8526, Japan.
authors: Xiaoxu
authors: X
authors: Zhao
authors: Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Suruga, Shizuoka, Shizuoka 422-8526, Japan.
authors: Yuko
authors: Y
authors: Ibuki
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D000090063:Proto-Oncogene Mas; D012834:Silver / Q000737:chemistry / Q000633:toxicity*
chemical_list: D006657:Histones; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012834:Silver