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Genotoxic effects of zinc oxide nanoparticles.
Nanoscale. 2015 May 21; 7(19):8931-8.N

Abstract

The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL(-1) using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn(2+) levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn(2+) with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn(2+) for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn(2+) may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn(2+) intake. Subsequently increased ROS-levels cause DNA damage. However, we found evidence for the assumption that DNA-DSBs could be caused by Zn(2+) without the involvement of ROS.

Authors+Show Affiliations

Molecular Tumorbiology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. juergen.brieger@unimedizin-mainz.de.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25916659

Citation

Heim, Julia, et al. "Genotoxic Effects of Zinc Oxide Nanoparticles." Nanoscale, vol. 7, no. 19, 2015, pp. 8931-8.
Heim J, Felder E, Tahir MN, et al. Genotoxic effects of zinc oxide nanoparticles. Nanoscale. 2015;7(19):8931-8.
Heim, J., Felder, E., Tahir, M. N., Kaltbeitzel, A., Heinrich, U. R., Brochhausen, C., Mailänder, V., Tremel, W., & Brieger, J. (2015). Genotoxic effects of zinc oxide nanoparticles. Nanoscale, 7(19), 8931-8. https://doi.org/10.1039/c5nr01167a
Heim J, et al. Genotoxic Effects of Zinc Oxide Nanoparticles. Nanoscale. 2015 May 21;7(19):8931-8. PubMed PMID: 25916659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotoxic effects of zinc oxide nanoparticles. AU - Heim,Julia, AU - Felder,Eva, AU - Tahir,Muhammad Nawaz, AU - Kaltbeitzel,Anke, AU - Heinrich,Ulf Ruediger, AU - Brochhausen,Christoph, AU - Mailänder,Volker, AU - Tremel,Wolfgang, AU - Brieger,Juergen, PY - 2015/4/29/entrez PY - 2015/4/29/pubmed PY - 2016/3/17/medline SP - 8931 EP - 8 JF - Nanoscale JO - Nanoscale VL - 7 IS - 19 N2 - The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL(-1) using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn(2+) levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn(2+) with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn(2+) for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn(2+) may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn(2+) intake. Subsequently increased ROS-levels cause DNA damage. However, we found evidence for the assumption that DNA-DSBs could be caused by Zn(2+) without the involvement of ROS. SN - 2040-3372 UR - https://www.unboundmedicine.com/medline/citation/25916659/Genotoxic_effects_of_zinc_oxide_nanoparticles_ L2 - https://doi.org/10.1039/c5nr01167a DB - PRIME DP - Unbound Medicine ER -