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Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations.

Kwon JY, Koedrith P, Seo YR - Int J Nanomedicine (2014)

Bottom Line: Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated.Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors.Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea.

ABSTRACT
Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.

No MeSH data available.


Related in: MedlinePlus

Scheme illustrating possible routes of cellular uptake, including passive diffusion, receptor-related endocytosis, and clarthrin- or caveolae-dependent endocytosis. In brief, nanoparticles are in the correct size and shape. They may dock on membrane receptors, facilitating receptor-mediated endocytosis. Alternatively, clathrin- or caveolae-mediated endocytosis may occur, which results in the formation of pits in the region of 120 nm or up to 80 nm, respectively, which regulates the size of the material they are able to enclose.
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f2-ijn-9-271: Scheme illustrating possible routes of cellular uptake, including passive diffusion, receptor-related endocytosis, and clarthrin- or caveolae-dependent endocytosis. In brief, nanoparticles are in the correct size and shape. They may dock on membrane receptors, facilitating receptor-mediated endocytosis. Alternatively, clathrin- or caveolae-mediated endocytosis may occur, which results in the formation of pits in the region of 120 nm or up to 80 nm, respectively, which regulates the size of the material they are able to enclose.

Mentions: If NPs are able to enter the body through inhalation, dermal, or oral routes, direct and indirect mechanisms exist to stimulate DNA damage.34,35,97 NPs may be able to penetrate into the cell, and subsequently the nucleus, through a number of routes (Figure 2).1 If NPs are located within the nucleus, direct interaction with DNA or DNA-associated proteins is possible. Indeed, silica NPs can enter the nucleus,98,99 inducing intranuclear protein aggregates and resulting in inhibition of replication, transcription, and cell proliferation.49,100,101 Quantum dots have also been shown to penetrate the nucleus via the nuclear pore complexes102 and interact with histone proteins.


Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations.

Kwon JY, Koedrith P, Seo YR - Int J Nanomedicine (2014)

Scheme illustrating possible routes of cellular uptake, including passive diffusion, receptor-related endocytosis, and clarthrin- or caveolae-dependent endocytosis. In brief, nanoparticles are in the correct size and shape. They may dock on membrane receptors, facilitating receptor-mediated endocytosis. Alternatively, clathrin- or caveolae-mediated endocytosis may occur, which results in the formation of pits in the region of 120 nm or up to 80 nm, respectively, which regulates the size of the material they are able to enclose.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279763&req=5

f2-ijn-9-271: Scheme illustrating possible routes of cellular uptake, including passive diffusion, receptor-related endocytosis, and clarthrin- or caveolae-dependent endocytosis. In brief, nanoparticles are in the correct size and shape. They may dock on membrane receptors, facilitating receptor-mediated endocytosis. Alternatively, clathrin- or caveolae-mediated endocytosis may occur, which results in the formation of pits in the region of 120 nm or up to 80 nm, respectively, which regulates the size of the material they are able to enclose.
Mentions: If NPs are able to enter the body through inhalation, dermal, or oral routes, direct and indirect mechanisms exist to stimulate DNA damage.34,35,97 NPs may be able to penetrate into the cell, and subsequently the nucleus, through a number of routes (Figure 2).1 If NPs are located within the nucleus, direct interaction with DNA or DNA-associated proteins is possible. Indeed, silica NPs can enter the nucleus,98,99 inducing intranuclear protein aggregates and resulting in inhibition of replication, transcription, and cell proliferation.49,100,101 Quantum dots have also been shown to penetrate the nucleus via the nuclear pore complexes102 and interact with histone proteins.

Bottom Line: Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated.Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors.Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea.

ABSTRACT
Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.

No MeSH data available.


Related in: MedlinePlus