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Effect of treatment media on size and cellular uptake of Ti02 nanoparticles: impact on genotoxicity in human respiratory cells.
Citation:
Prasad, R. Y., K. Wallace, A. H. Tennant, A. D. Kligerman, C. F. BLACKMAN, D. M. DEMARINI, AND R. M. Zucker. Effect of treatment media on size and cellular uptake of Ti02 nanoparticles: impact on genotoxicity in human respiratory cells. Presented at NC Society of Toxicology Spring Meeting, Research Triangle Park, NC, February 23, 2012.
Impact/Purpose:
The widespread use of titanium dioxide (Ti02) nanoparticles in consumer products increases the probability of exposure to humans and the environment. Although Ti02 nanoparticles have been shown to induce DNA damage and micronuclei in vitro, no study has systematically assessed the influence of medium composition on particle agglomeration, cellular uptake, and genotoxicity of Ti02 nanoparticles
Description:
The widespread use of titanium dioxide (Ti02) nanoparticles in consumer products increases the probability of exposure to humans and the environment. Although Ti02 nanoparticles have been shown to induce DNA damage and micronuclei in vitro, no study has systematically assessed the influence of medium composition on particle agglomeration, cellular uptake, and genotoxicity of Ti02 nanoparticles. Here, we assessed Ti02 nanoparticle agglomeration, cellular uptake, and genotoxicity (DNA damage analyzed via the comet assay and chromosomal damage measured by the micronucleus assay) in human lung epithelial cells using three different media: KGM medium plus 0.1% bovine serum albumin (KB), a broncheoalveolar lavage synthetic fluid containing 0.6% bovine serum albumin and 0.01% surfactant (DM), or KGM medium supplemented with 10% fetal bovine serum (KF). Using flow cytometry we found that KF medium facilitated the greatest particle uptake. Ti02 nanoparticles induced DNA damage in cells treated in all three media, and this induction was not influenced by either agglomeration or cellular uptake as measured by flow cytometry. Ti02 nanoparticles induced micronuclei due to chromosome breakage in KF; however, they did not induce micronuclei in KB and DM. Thus, chromosome breakage required cellular uptake presumably resulting in a direct interaction of particles with chromatin. These studies demonstrate a clear dependence on cellular uptake and protein-nanoparticle interaction for Ti02 nanoparticles to lead to the induction of chromosomal damage as measured by the micronucleus assay. In contrast, the DNA damage measured by the comet assay induced by Ti02 nanoparticles does not require particle uptake and likely occurs via indirect mechanisms such as reactive oxygen species generated extracellularly. [This abstract or proposed presentation does not reflect EPA policy].