Document Detail

Nano-scaled particles of titanium dioxide convert benign mouse fibrosarcoma cells into aggressive tumor cells.
MedLine Citation:
PMID:  19815711     Owner:  NLM     Status:  MEDLINE    
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.
Kunishige Onuma; Yu Sato; Satomi Ogawara; Nobuyuki Shirasawa; Masanobu Kobayashi; Jun Yoshitake; Tetsuhiko Yoshimura; Masaaki Iigo; Junichi Fujii; Futoshi Okada
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-08
Journal Detail:
Title:  The American journal of pathology     Volume:  175     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-02     Completed Date:  2010-01-11     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2171-83     Citation Subset:  AIM; IM    
Department of Biochemistry and Molecular Biology, Yamagata University, Japan.
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MeSH Terms
Cell Line, Tumor
Cell Transformation, Neoplastic / drug effects*
Cytokines / genetics,  metabolism
Deoxyguanosine / analogs & derivatives,  metabolism
Dinoprostone / metabolism
Fibrosarcoma* / metabolism,  pathology
Intercellular Signaling Peptides and Proteins / genetics,  metabolism
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
Reg. No./Substance:
0/8-hydroxy-2'-deoxyguanosine; 0/Cytokines; 0/Intercellular Signaling Peptides and Proteins; 0/Reactive Oxygen Species; 0/Vascular Endothelial Growth Factor A; 15FIX9V2JP/titanium dioxide; 363-24-6/Dinoprostone; 61512-21-8/Thymosin; 7440-32-6/Titanium; 77591-33-4/thymosin beta(4); 961-07-9/Deoxyguanosine

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