2015 Volume 80 Issue 2 Pages 173-181
Gold nanoparticles (GNPs) shall be applied in cancer therapy, conceivably by using a simple injection of GNPs into human veins. This will bring them in contact with red and white blood cells of the blood stream before they reach their main target, the cancer cells. However, possible cyto- and/or genotoxic effects of GNPs on lymphocytes are not known in detail and are thus studied here. Cytotoxicity was determined by Trypan blue exclusion assay. For genotoxicity, Comet and Comet-FISH (=fluorescence in situ hybridization) assays were done. In the latter test two gene markers for DNA damage, TP53 as tumor suppressor gene and TNF-α as tumor necrosis factor gene, were investigated. The cells were incubated in the presence of different concentrations of polyethylene glycol–coated rod-shaped GNPs of 50 nm or 30 nm in diameter. GNPs induced cytotoxic effects in human lymphocytes. The effects could be observed in concentration- and size-dependent manner; 30 nm sized GNPs were more toxic than 50 nm sized ones. Using the comet assay, it was demonstrated that GNPs induce high rates of DNA damage, which are represented e.g. as high ratios of tail moments, compared to non-treated lymphocytes. The target genes (TP53 and TNF-α) were observed preferentially in comet tails indicating high rates of induced DNA damage in this DNA area. Our results suggest that rod-shaped GNPs interact with human blood lymphocytes, reduce cell viability and cause relevant DNA damage in a concentration dependent manner. The small sized GNPs were more cyto- and genotoxic than big sized GNPs. The low concentration of big sized rod-shaped GNPs could be safe for cancer photothermal therapy rather than small rod GNPs. However, further investigations are recommended to be able to minimize potential risks of application.
