Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts.
Summary of "Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts."
Abstract The use of nanoparticles in consumer products increases their prevalence in the environment and the potential risk to human health. Although recent studies have shown in vivo and in vitro toxicity of titanium dioxide nanoparticles (nano-TiO(2)), a more detailed view of the underlying mechanisms of this response needs to be established. Here the effects of nano-TiO(2) on the DNA damage response and DNA replication dynamics were investigated in human dermal fibroblasts. Specifically, the relationship between nano-TiO(2) and the DNA damage response pathways regulated by ATM/Chk2 and ATR/Chk1 were examined. The results show increased phosphorylation of H2AX, ATM, and Chk2 after exposure. In addition, nano-TiO(2) inhibited the overall rate of DNA synthesis and frequency of replicon initiation events in DNA combed fibers. Taken together, these results demonstrate that exposure to nano-TiO(2) activates the ATM/Chk2 DNA damage response pathway.
Affiliation
Department of Environmental Sciences and Engineering , Gillings School of Global Public Health, University of North Carolina, Chapel Hill , NC.
Journal Details
This article was published in the following journal.
Name: Nanotoxicology
ISSN: 1743-5404
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22770119
- DOI: http://dx.doi.org/10.3109/17435390.2012.710659
Medical and Biotech [MESH] Definitions
Nanoparticles
Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.
Metal Nanoparticles
Nanoparticles produced from metals whose uses include biosensors, optics, and catalysts. In biomedical applications the particles frequently involve the noble metals, especially gold and silver.
Nijmegen Breakage Syndrome
A chromosome instability syndrome resulting from a defective response to DNA double-strand breaks. In addition to characteristic FACIES and MICROCEPHALY, patients have a range of findings including RADIOSENSITIVITY, immunodeficiency, increased cancer risk, and growth retardation. Causative mutations occur in the NBS1 gene, located on human chromosome 8q21. NBS1 codes for nibrin, the key regulator protein of the R/M/N (RAD50/MRE11/NBS1) protein complex which senses and mediates cellular response to DNA DAMAGE caused by IONIZING RADIATION.
Phosphoenolpyruvate Carboxylase
An enzyme with high affinity for carbon dioxide. It catalyzes irreversibly the formation of oxaloacetate from phosphoenolpyruvate and carbon dioxide. This fixation of carbon dioxide in several bacteria and some plants is the first step in the biosynthesis of glucose. EC 4.1.1.31.
Adjuvants, Immunologic
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
PubMed Articles
Exposure to titanium dioxide nanoparticles induces autophagy in primary human keratinocytes.
Understanding the mechanisms of cell-nanomaterial interactions is vital in harnessing the potential of using nanomaterials in biomedical applications. By immuno-labeling of LC3 and TEM analysis, it is...
Photodeposition of Ag or Pt onto TiO(2) Nanoparticles Decorated on Step Edges of HOPG.
Ordered linear arrays of titanium dioxide nanoparticles were fabricated on highly oriented pyrolytic graphite utilizing a step edge decoration method. Ag- or Pt-based nanoparticles were then photodepo...
Myc is a transcription factor frequently found deregulated in human cancer. The Myc-mediated cellular transformation process is associated with fast proliferative cells and inherent genomic instabilit...
Centrosomal Chk2 in DNA damage responses and cell cycle progession.
Two major control systems regulate early stages of mitosis: activation of Cdk1 and anaphase control through assembly and disassembly of the mitotic spindle. In parallel to cell cycle progression, cent...
Targeted drug delivery using nanocrystalline materials delivers the drug at the deseased site. This increases the efficacy of the drug in killing the cancer cells. Surface modifications were done to t...
Clinical Trials
The effects on indices of gingivitis/periodontitis will differ between study arms in which the titanium dioxide semiconductor toothbrush is used, compared to an otherwise identical toothbr...
The Cyclocapnic Method for Measurement of Chemosensitivity
We aim to test our method for measuring chemosensitivity (the ventilatory response to a change in carbon dioxide), which uses sinusoidal carbon dioxide stimuli. Hypotheses: - Ca...
The aim of this study is to evaluate the antibacterial activity of crosslinked quaternary ammonium polyethylenimine (PEI) nanoparticles incorporated at 1-2% w/w in a commercial soft liner...
The effect of Antibacterial Nanoparticles, Incorporated in cement, on S.mutans in the margins of provisional restorations is going to be examined clinically by using two kinds of provision...
RESTIT : Evaluation of Resorbable Osteosynthesis Devices Versus Titanium in Maxillofacial Surgery
Primary objective : To evaluate the quality of fractures setting and osteotomy of the facial massif osteosynthesised with resorbable device PLLA/PGA compared with usual Titanium plates....
