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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

Putative mechanisms underlying the detrimental effects of zinc oxide and silica nanoparticles. These nanoparticles dissolve in the extracellular milieu, giving rise to increased extracellular metallic cations. This leads to increased intracellular respective metallic cations, resulting in decreased activity of particular enzymes and transcription factors. Moreover, this event can induce ROS generation and resulting oxidative stress, as well as stimulate various cytokine production and inflammatory responses. These phenomena, in turn, render membrane damage, DNA breakage, mitochondrial dysfunction, and lysosome destabilization.Abbreviations: ROS, reactive oxygen species; RNS, reactive nitrogen species; IL, interleukin; TNF, tumor necrosis factor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; MAPK, mitogen-activated protein kinases; AP-1, activator protein 1.
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f4-ijn-9-271: Putative mechanisms underlying the detrimental effects of zinc oxide and silica nanoparticles. These nanoparticles dissolve in the extracellular milieu, giving rise to increased extracellular metallic cations. This leads to increased intracellular respective metallic cations, resulting in decreased activity of particular enzymes and transcription factors. Moreover, this event can induce ROS generation and resulting oxidative stress, as well as stimulate various cytokine production and inflammatory responses. These phenomena, in turn, render membrane damage, DNA breakage, mitochondrial dysfunction, and lysosome destabilization.Abbreviations: ROS, reactive oxygen species; RNS, reactive nitrogen species; IL, interleukin; TNF, tumor necrosis factor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; MAPK, mitogen-activated protein kinases; AP-1, activator protein 1.

Mentions: Genotoxicity may arise through indirect mechanisms where NPs do not physically interact with the DNA molecule but with other cellular components, such as those involved in the cell division process. Other cellular responses may be induced and give rise to genotoxicity, such as oxidative stress induction, inflammatory response, and aberrant signaling responses (Figure 3).1,35,97 Moreover, putative mechanisms underlying the detrimental effects of ZnO and silica NPs are proposed (Figure 4).


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)

Putative mechanisms underlying the detrimental effects of zinc oxide and silica nanoparticles. These nanoparticles dissolve in the extracellular milieu, giving rise to increased extracellular metallic cations. This leads to increased intracellular respective metallic cations, resulting in decreased activity of particular enzymes and transcription factors. Moreover, this event can induce ROS generation and resulting oxidative stress, as well as stimulate various cytokine production and inflammatory responses. These phenomena, in turn, render membrane damage, DNA breakage, mitochondrial dysfunction, and lysosome destabilization.Abbreviations: ROS, reactive oxygen species; RNS, reactive nitrogen species; IL, interleukin; TNF, tumor necrosis factor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; MAPK, mitogen-activated protein kinases; AP-1, activator protein 1.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-9-271: Putative mechanisms underlying the detrimental effects of zinc oxide and silica nanoparticles. These nanoparticles dissolve in the extracellular milieu, giving rise to increased extracellular metallic cations. This leads to increased intracellular respective metallic cations, resulting in decreased activity of particular enzymes and transcription factors. Moreover, this event can induce ROS generation and resulting oxidative stress, as well as stimulate various cytokine production and inflammatory responses. These phenomena, in turn, render membrane damage, DNA breakage, mitochondrial dysfunction, and lysosome destabilization.Abbreviations: ROS, reactive oxygen species; RNS, reactive nitrogen species; IL, interleukin; TNF, tumor necrosis factor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; MAPK, mitogen-activated protein kinases; AP-1, activator protein 1.
Mentions: Genotoxicity may arise through indirect mechanisms where NPs do not physically interact with the DNA molecule but with other cellular components, such as those involved in the cell division process. Other cellular responses may be induced and give rise to genotoxicity, such as oxidative stress induction, inflammatory response, and aberrant signaling responses (Figure 3).1,35,97 Moreover, putative mechanisms underlying the detrimental effects of ZnO and silica NPs are proposed (Figure 4).

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