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Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts.

Lai JC, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, Leung SW - Int J Nanomedicine (2008)

Bottom Line: Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts.We further noted that zinc oxide (ZnO) nanoparticles were the most effective, TiO(2) nanoparticles the second most effective, and magnesium oxide (MgO) nanoparticles the least effective in inducing cell death in U87 cells.Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Pocatello, ID 83209, USA.

ABSTRACT
The use of titanium dioxide (TiO(2)) in various industrial applications (eg, production of paper, plastics, cosmetics, and paints) has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO(2) nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO(2) micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO) nanoparticles were the most effective, TiO(2) nanoparticles the second most effective, and magnesium oxide (MgO) nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO(2) micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.

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Increases in Annexin-V-stained cells after exposure of human astrocytoma (astrocytes-like) U87 cells to TiO2 microparticles or nanoparticles.Notes: U87 cells were treated with TiO2 microparticles or nanoparticles for 48 hours, then stained with Annexin-V, and the stained cells were photographed at a magnification of 100. The treatments were: A) control (ie, untreated) U87 cells; B) cells treated with 1 μg/mL TiO2 microparticles; C) cells treated with 10 μg/mL TiO2 microparticles; D) cells treated with 50 μg/mL TiO2 microparticles; E) cells treated with 1 μg/mL TiO2 nanoparticles; F) cells treated with 10 μg/mL TiO2 nanoparticles; and G) cells treated with 50 μg/mL TiO2 nanoparticles. Cells marked with < or > were co-stained with both Annexin-V and PI.Abbreviations: PI, propidium iodide; TiO2, titanium dioxide.
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f6-ijn-3-533: Increases in Annexin-V-stained cells after exposure of human astrocytoma (astrocytes-like) U87 cells to TiO2 microparticles or nanoparticles.Notes: U87 cells were treated with TiO2 microparticles or nanoparticles for 48 hours, then stained with Annexin-V, and the stained cells were photographed at a magnification of 100. The treatments were: A) control (ie, untreated) U87 cells; B) cells treated with 1 μg/mL TiO2 microparticles; C) cells treated with 10 μg/mL TiO2 microparticles; D) cells treated with 50 μg/mL TiO2 microparticles; E) cells treated with 1 μg/mL TiO2 nanoparticles; F) cells treated with 10 μg/mL TiO2 nanoparticles; and G) cells treated with 50 μg/mL TiO2 nanoparticles. Cells marked with < or > were co-stained with both Annexin-V and PI.Abbreviations: PI, propidium iodide; TiO2, titanium dioxide.

Mentions: As observed under fluorescence microscopy, very few control (ie, untreated) U87 cells were stained with Annexin-V (Figure 6A), indicating that there were very few apoptotic cells within that population. After U87 cells had been treated with progressively increased concentrations of TiO2 microparticles (1, 10, or 50 μg/mL) for 48 hours, the number of cells stained with Annexin-V progressively increased (Figures 6B–6D), suggesting that the number of apoptotic cells increased with increases in treatment levels. It is interesting to note that not all the treated cells showed uniformed staining although the staining intensity increased as the treatment level increased (Figures 6B–6D) suggesting that the microparticle-induced apoptosis was not synchronized in those populations of U87 cells. Similarly, after U87 cells had been treated with progressively increased concentrations of TiO2 nanoparticles (1, 10, or 50 μg/mL) for 48 hours, the number of cells stained with Annexin-V progressively increased (Figures 6E–6G), suggesting that the number of apoptotic cells increased with increases in treatment levels. However, the level of Annexin-V staining in the nanoparticles-treated cells was less marked compared to those in cells treated with corresponding levels of microparticles (Figures 6B–6D). Again, we noticed that both TiO2 microparticles and nanoparticles interacted with the Annexin-V dye to yield some fluorescence in the absence of U87 cells, although their fluorescence was minimal (data not shown). Furthermore, it was interesting to observe that many U87 cells treated with TiO2 microparticles or nanoparticles stained with Annexin-V also co-stained with PI (compare Figures 5 and 6) while in the same field there were few treated cells that stained only with Annexin-V or PI, suggesting either apoptosis and necrosis mechanisms were co-occurring in those cells or those cells exhibited another cell death mechanism that shares some common features with apoptosis and necrosis (ie, hybrid mechanism; Bröker et al 2005; Wei et al 2006; Golstein and Kroemer 2007).


Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts.

Lai JC, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, Leung SW - Int J Nanomedicine (2008)

Increases in Annexin-V-stained cells after exposure of human astrocytoma (astrocytes-like) U87 cells to TiO2 microparticles or nanoparticles.Notes: U87 cells were treated with TiO2 microparticles or nanoparticles for 48 hours, then stained with Annexin-V, and the stained cells were photographed at a magnification of 100. The treatments were: A) control (ie, untreated) U87 cells; B) cells treated with 1 μg/mL TiO2 microparticles; C) cells treated with 10 μg/mL TiO2 microparticles; D) cells treated with 50 μg/mL TiO2 microparticles; E) cells treated with 1 μg/mL TiO2 nanoparticles; F) cells treated with 10 μg/mL TiO2 nanoparticles; and G) cells treated with 50 μg/mL TiO2 nanoparticles. Cells marked with < or > were co-stained with both Annexin-V and PI.Abbreviations: PI, propidium iodide; TiO2, titanium dioxide.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2636591&req=5

f6-ijn-3-533: Increases in Annexin-V-stained cells after exposure of human astrocytoma (astrocytes-like) U87 cells to TiO2 microparticles or nanoparticles.Notes: U87 cells were treated with TiO2 microparticles or nanoparticles for 48 hours, then stained with Annexin-V, and the stained cells were photographed at a magnification of 100. The treatments were: A) control (ie, untreated) U87 cells; B) cells treated with 1 μg/mL TiO2 microparticles; C) cells treated with 10 μg/mL TiO2 microparticles; D) cells treated with 50 μg/mL TiO2 microparticles; E) cells treated with 1 μg/mL TiO2 nanoparticles; F) cells treated with 10 μg/mL TiO2 nanoparticles; and G) cells treated with 50 μg/mL TiO2 nanoparticles. Cells marked with < or > were co-stained with both Annexin-V and PI.Abbreviations: PI, propidium iodide; TiO2, titanium dioxide.
Mentions: As observed under fluorescence microscopy, very few control (ie, untreated) U87 cells were stained with Annexin-V (Figure 6A), indicating that there were very few apoptotic cells within that population. After U87 cells had been treated with progressively increased concentrations of TiO2 microparticles (1, 10, or 50 μg/mL) for 48 hours, the number of cells stained with Annexin-V progressively increased (Figures 6B–6D), suggesting that the number of apoptotic cells increased with increases in treatment levels. It is interesting to note that not all the treated cells showed uniformed staining although the staining intensity increased as the treatment level increased (Figures 6B–6D) suggesting that the microparticle-induced apoptosis was not synchronized in those populations of U87 cells. Similarly, after U87 cells had been treated with progressively increased concentrations of TiO2 nanoparticles (1, 10, or 50 μg/mL) for 48 hours, the number of cells stained with Annexin-V progressively increased (Figures 6E–6G), suggesting that the number of apoptotic cells increased with increases in treatment levels. However, the level of Annexin-V staining in the nanoparticles-treated cells was less marked compared to those in cells treated with corresponding levels of microparticles (Figures 6B–6D). Again, we noticed that both TiO2 microparticles and nanoparticles interacted with the Annexin-V dye to yield some fluorescence in the absence of U87 cells, although their fluorescence was minimal (data not shown). Furthermore, it was interesting to observe that many U87 cells treated with TiO2 microparticles or nanoparticles stained with Annexin-V also co-stained with PI (compare Figures 5 and 6) while in the same field there were few treated cells that stained only with Annexin-V or PI, suggesting either apoptosis and necrosis mechanisms were co-occurring in those cells or those cells exhibited another cell death mechanism that shares some common features with apoptosis and necrosis (ie, hybrid mechanism; Bröker et al 2005; Wei et al 2006; Golstein and Kroemer 2007).

Bottom Line: Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts.We further noted that zinc oxide (ZnO) nanoparticles were the most effective, TiO(2) nanoparticles the second most effective, and magnesium oxide (MgO) nanoparticles the least effective in inducing cell death in U87 cells.Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Pocatello, ID 83209, USA.

ABSTRACT
The use of titanium dioxide (TiO(2)) in various industrial applications (eg, production of paper, plastics, cosmetics, and paints) has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO(2) nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO(2) micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO) nanoparticles were the most effective, TiO(2) nanoparticles the second most effective, and magnesium oxide (MgO) nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO(2) micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.

Show MeSH
Related in: MedlinePlus