Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549

Abstract

Nanomaterials, especially silver nanoparticles (Ag NPs), are used in a rapidly increasing number of commercial products. Accordingly, the hazards associated with human exposure to nanomaterials should be investigated to facilitate the risk assessment process. A potential route of exposure to NPs is through the respiratory system. In the present study, we investigated the effects of well-characterized PVP-coated Ag NPs and silver ions (Ag+) in the human, alveolar cell line, A549. Dose-dependent cellular toxicity caused by Ag NPs and Ag+ was demonstrated by the MTT and annexin V/propidium iodide assays, and evidence of Ag NP uptake could be measured indirectly by atomic absorption spectroscopy and flow cytometry. The cytotoxicity of both silver compounds was greatly decreased by pretreatment with the antioxidant, N-acetyl-cysteine, and a strong correlation between the levels of reactive oxygen species (ROS) and mitochondrial damage (r(s) = -0.8810; p = 0.0039) or early apoptosis (r(s) = 0.8857; p = 0.0188) was observed. DNA damage induced by ROS was detected as an increase in bulky DNA adducts by (32)P postlabeling after Ag NP exposure. The level of bulky DNA adducts was strongly correlated with the cellular ROS levels (r(s) = 0.8810, p = 0.0039) and could be inhibited by antioxidant pretreatment, suggesting Ag NPs as a mediator of ROS-induced genotoxicity.

Nanoparticles attenuate P-glycoprotein/MDR1 function in A549 human alveolar epithelial cells

“…Thus, whilst nanoparticles potentially change the conformation of the cell membrane, resulting in a disruption of cellular processes and membrane integrity [23,24], most interactions with the cell membrane do not cause any membrane disruption or extraction of the protein from the plasmalemma, as previously observed in the case of cyclodextrins [25]. This was confirmed by Western blot analysis of the cells and their supernatant.…”

(Q)SAR modelling of nanomaterial toxicity: A critical review

“…Another important example of the ENM which raises toxicological concerns due to its widespread use in consumer products is nano-silver. Although nano-silver was known to be harmless, recent studies (Asare, et al, 2012;Foldbjerg, Dang, & Autrup, 2011;Hussain, et al, 2006;Kim, et al, 2009) have provided convincing evidence of toxicity associated with the exposure to nano-silver. More detailed information about the potential adverse effects of various NMs has been provided by several researchers (Arora, et al, 2012;Holgate, 2010;Horie & Fujita, 2011;Jeng & Swanson, 2006;Magrez, et al, 2006;Saquib, et al, 2012;Sharifi, et al, 2012;Wani, Hashim, Nabi, & Malik, 2011).…”

Silver nanoparticles induce cytotoxicity, but not cell transformation or genotoxicity on Balb3T3 mouse fibroblasts

“…Colloidal aqueous suspension of spherical Ag NPs of 7-20 nm induce cytotoxicity on primary mouse fibroblasts and primary liver cells; moreover they induce oxidative stress as reduction in the glutathione (GSH) level, and increase of reactive oxygen species (ROS) and lipid peroxidation on human skin carcinoma cells (A431) and human fibrosarcoma cells (HT-1080) [9,10]. PVP-coated Ag NPs of 30-50 nm and starch-coated Ag NPs of 6-20 nm induce ROS production on human alveolar cell line (A549), on human lung fibroblasts cells (IMR-90) and on human glioblastoma cells (U251), respectively [11,12], and for starch-coated Ag NPs, a reduction in the ATP content and DNA damage are also noted [12]. Ag nano-spheres of 30 nm were found to be cytotoxic and genotoxic on medaka fish cell line (OLHNI2) [13].…”