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One low-dose exposure of gold nanoparticles induces long-term changes in human cells.

ABSTRACT: We report the in vitro long-term (20 wk) changes in cells exposed to well-characterized gold nanoparticles (Au NPs) with varying shapes and surface coatings under both chronic (exposure to Au NPs continuously over 20 wk) and nonchronic (initial acute cell exposure to Au NPs, followed by 20 wk in NP-free cell media) conditions. Both chronic and nonchronic Au NPs exposures at low dose induce modifications at the gene level after long periods. In attempt to overcome from the injuries caused by nanoparticle exposure, genes related to oxidative stress, cell cycle regulation, and inflammation are among those presenting differential expression levels. Surprisingly, the nonchronic exposure induced more gene expression changes than its chronic counterpart and the stress effects caused by this type of exposure were sustained even after 20 wk without any additional NP exposure. NP surface chemistry played an important role in the alteration of gene regulation. Overall, our data suggest that (i) cells can adaptively respond to chronic, low-level NP insults; (ii) the cell stress response is not reversible over time upon removal of NPs upon acute, nonchronic exposure; and (iii) polyethylene glycol is not as benign a surface chemistry as is generally supposed.

SUBMITTER: Falagan-Lotsch P

PROVIDER: S-EPMC5127334 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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One low-dose exposure of gold nanoparticles induces long-term changes in human cells.

Falagan-Lotsch Priscila P Grzincic Elissa M EM Murphy Catherine J CJ

Proceedings of the National Academy of Sciences of the United States of America 20161107 47

We report the in vitro long-term (20 wk) changes in cells exposed to well-characterized gold nanoparticles (Au NPs) with varying shapes and surface coatings under both chronic (exposure to Au NPs continuously over 20 wk) and nonchronic (initial acute cell exposure to Au NPs, followed by 20 wk in NP-free cell media) conditions. Both chronic and nonchronic Au NPs exposures at low dose induce modifications at the gene level after long periods. In attempt to overcome from the injuries caused by nano ...[more]

PMID: 27821760

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Project description:There is an increasing need to better understand the long-term health effects of high-linear energy transfer (LET) radiation due to exposure during space missions, as well as its increasing use in clinical treatments. Previous studies have indicated that exposure to (56)Fe heavy ions increases the incidence of acute myeloid leukemia (AML) in mice but the underlying molecular mechanisms remain elusive. Epigenetic alterations play a role in radiation-induced genomic instability and the initiation and progression of AML. In this study, we assessed the effects of low-dose (56)Fe-ion irradiation on epigenetic alterations in bone marrow mononuclear cells (BM-MNCs) and hematopoietic progenitor and stem cells (HPSCs). Exposure to (56)Fe ions (600 MeV, 0.1, 0.2 and 0.4 Gy) resulted in significant epigenetic alterations involving methylation of DNA, the DNA methylation machinery and expression of repetitive elements. Four weeks after irradiation, these changes were primarily confined to HPSCs and were exhibited as dose-dependent hypermethylation of LINE1 and SINE B1 repetitive elements [4.2-fold increase in LINE1 (P < 0.001) and 7.6-fold increase in SINE B1 (P < 0.01) after exposure to 0.4 Gy; n = 5]. Epigenetic alterations were persistent and detectable for at least 22 weeks after exposure, when significant loss of global DNA hypomethylation (1.9-fold, P < 0.05), decreased expression of Dnmt1 (1.9-fold, P < 0.01), and increased expression of LINE1 and SINE B1 repetitive elements (2.8-fold, P < 0.001 for LINE1 and 1.9-fold, P < 0.05 for SINE B1; n = 5) were observed after exposure to 0.4 Gy. In contrast, exposure to (56)Fe ions did not result in accumulation of increased production of reactive oxygen species (ROS) and DNA damage, exhibited as DNA strand breaks. Furthermore, no significant alterations in cellular senescence and apoptosis were detected in HPSCs after exposure to (56)Fe-ion radiation. These findings suggest that epigenetic reprogramming is possibly involved in the development of radiation-induced genomic instability and thus, may have a causative role in the development of AML.

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One low-dose exposure of gold nanoparticles induces long-term changes in human cells.

Publications

One low-dose exposure of gold nanoparticles induces long-term changes in human cells.

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