| Nano-scaled particles of titanium dioxide convert benign mouse fibrosarcoma cells into aggressive tumor cells. | |
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MedLine Citation:
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PMID: 19815711 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO(2)) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO(2), either uncoated (TiO(2)-1, hydrophilic) or coated with stearic acid (TiO(2)-2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO(2)-1, but not TiO(2)-2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO(2)-1 and TiO(2)-2 treatments. However, TiO(2)-2, but not TiO(2)-1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO(2)-1 and TiO(2)-2 resulted in intracellular ROS formation, TiO(2)-2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO(2)-2, but not TiO(2)-1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO(2) toxicity acquired a tumorigenic phenotype. TiO(2)-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO(2) has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells. |
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Authors:
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Kunishige Onuma; Yu Sato; Satomi Ogawara; Nobuyuki Shirasawa; Masanobu Kobayashi; Jun Yoshitake; Tetsuhiko Yoshimura; Masaaki Iigo; Junichi Fujii; Futoshi Okada |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-08 |
Journal Detail:
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Title: The American journal of pathology Volume: 175 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-11-02 Completed Date: 2010-01-11 Revised Date: 2010-11-02 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 2171-83 Citation Subset: AIM; IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Yamagata University, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Tumor Cell Transformation, Neoplastic / drug effects* Cytokines / genetics, metabolism Deoxyguanosine / analogs & derivatives, metabolism Dinoprostone / metabolism Female Fibrosarcoma* / metabolism, pathology Intercellular Signaling Peptides and Proteins / genetics, metabolism Mice Mice, Inbred C57BL Nanoparticles / chemistry* Neoplasm Invasiveness* / pathology Particle Size Reactive Oxygen Species / metabolism Thymosin / genetics, metabolism Titanium / chemistry, pharmacology* Vascular Endothelial Growth Factor A / metabolism |
| Chemical | |
Reg. No./Substance:
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0/8-hydroxy-2'-deoxyguanosine; 0/Cytokines; 0/Intercellular Signaling Peptides and Proteins; 0/Reactive Oxygen Species; 0/Vascular Endothelial Growth Factor A; 13463-67-7/titanium dioxide; 363-24-6/Dinoprostone; 61512-21-8/Thymosin; 7440-32-6/Titanium; 77591-33-4/thymosin beta(4); 961-07-9/Deoxyguanosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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