Researchers from the University of Dayton have completed the first study of its kind evaluating the potential toxicity of nanomaterials on the molecular level. Previous studies of nanomaterial safety conducted on the cellular level were shown to be safe. This time the results are somewhat different.
“Our results suggest that careful scrutiny of the genotoxicity of nanomaterials is needed even for those materials, like multi-walled carbon nanotubes, that have been previously demonstrated to have limited or no toxicity at the cellular level” Dr. Liming Dai tells Nanowerk. “The results of our study also provide strong support for the use of p53 as a biomarker for preliminary screening of genotoxicity of nanomaterials.”
Dai explains that, in response to DNA damage, eukaryotic cells, including ES cells, have developed several mechanisms to protect genomic integrity. In the presence of damaged DNA for instance, the p53 protein is activated by protein phosphorylation as a master guardian that activates cell cycle checkpoints and triggers cell cycle arrest to provide time for the DNA damage to be repaired.
“Enhanced expression of p53 may also trigger cell death by apoptosis if the DNA damage is beyond repair, while under normal conditions (absence of DNA damage) p53 is expressed at low levels” he says. “The close relationship between p53 activation and DNA damage makes p53 the molecular marker of choice for assessing the genotoxicity of MWCNTs [multi-walled carbon nanotubes –ed.] to mouse ES cells…”
As the researchers report in their paper in the November 29, 2007 online edition of Nano Letters (“DNA Damage Induced by Multi-walled Carbon Nanotubes in Mouse Embryonic Stem Cells“), the DNA damage induced by MWCNTs was indicated by Western blot analysis of 8-oxoguanine-DNA glycosylase 1 (OGG1) and by the induction of two key double-strand break repair proteins, Rad 51 and XRCC4. Furthermore, the MWCNT treatment was found to cause a two-fold increase in the mutation frequency in mouse ES cells.
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