In vitro genotoxic effects of ZnO nanomaterials in human peripheral lymphocytes

Abstract

In this study, possible genotoxic effects of zinc oxide (ZnO) nanoparticles were investigated in cultured human peripheral lymphocytes by using chromosome aberrations and micronucleus assays (MN). For this purpose, the cells were treated with ZnO (1, 2, 5, 10, 15 and 20 lg/mL) for 24 and 48 h. In this research, four types of chromosome aberrations were observed as chromatid and chromosome breaks, fragment and dicentric chromosomes. ZnO induced significant increase of the ratio of chromosomal aberrations as well as percentage of abnormal cells at concentrations of 1, 5, 10 and 20 lg/mL in 24 h treatments. In 48 h treatments, while ZnO nanomaterials induced significant increase of the percentage of abnormal cells only at a concentration of 10 lg/mL, and of chromosome aberration per cell in comparison to the control at concentrations of 5 and 10 lg/mL. On the other hand, this material significantly increased the micronuclei frequency (MN) at concentrations of 10 and 15 lg/mL in comparison to the control. Cytokinesis-block proliferation index was not affected by ZnO treatments. It also decreased the mitotic index in all concentrations at 24 h but not at 48 h. The present results indicate that ZnO nanoparticles are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro at specific concentrations and time periods.

Investigation of the Genotoxicity of Aluminum Oxide, β-Tricalcium Phosphate, and Zinc Oxide Nanoparticles In Vitro

“…41 –47 The previous studies reported that ZnO NPs induced DNA double-strand breaks frequency, olive tail moment, apoptosis, DNA breaks, and CA frequency on A549, HEK, HepG2, MEF Ogg1 +/+ , CHO, and human peripheral lymphocyte cells in the concentration range of 0.1 to 320 µg/mL. 23,48 –52 Similarly, our findings also demonstrated that ZnO NPs caused genotoxicity on human lymphocytes in the concentration range of 12.5 to 250 ppm. The ZnO NPs also caused cell death at 500 to 2000 ppm dose range; therefore, no cells were counted at these concentrations.…”

Assessment of the genotoxic potential of two zinc oxide sources (amorphous and nanoparticles) using the in vitro micronucleus test and the in vivo wing somatic mutation and recombination test

“…When investigated in cultured human peripheral lymphocytes, ZnO NPs significantly increased the MN frequency at concentrations of 10 and 15 g/mL compared with that in the control. However, lower concentrations (<10 g/mL) did not induce significant alterations in the MN frequency ( Gümüs et al, 2014). ZnO NPs and its bulky forms evaluated in human embryonic kidney (HEK293) and mouse embryonic fibroblast (NIH/3T3) cells were able to increase significantly the number of MNs at doses up 100 µg/mL (Demir et al, 2014).…”

“…The authors suggested that this could be due to an increased aggregation of ZnO NPs at high concentrations in the lymphocyte culture. Therefore, the addition of increasing concentrations/doses of ZnO NPs to lymphocyte cultures may not be paralleled by an equivalent increase in the genotoxic effects of this nanomaterial ( Gümüs et al, 2014).…”

“…The in vitro MN assay can detect chromosomal damage in the form of clastogenicity induced by ROS, one of the main mechanisms of NP genotoxicity (Pfuhler et al, 2013). The CBMN has been widely accepted to screen ZnO NPs for genotoxicity in different cell lines (Osman et al, 2010;Corradi et al, 2012;Wahab et al, 2013;Bhattacharya et al, 2014;Demir et al, 2014;Gümüs et al, 2014).…”

Metal Nanomaterials: Immune Effects and Implications of Physicochemical Properties on Sensitization, Elicitation, and Augmentation of Allergic Disease

“…Although selective cytotoxic effects on lymphocytes is an immunotoxic effect most frequently associated with immunosuppressive responses, a similar effect could be associated with implications for allergic conditions, as well (1121). Accordingly, metal nanomaterial cytotoxic and genotoxic effects have been investigated in murine and human lymphocytes in vitro and correlated to properties including size and morphology (1122)(1123)(1124)(1125)(1126)(1127)(1128). Interestingly, lymphocytes have been demonstrated to be more resistant to adverse effects of ZnONP compared to other immune cell types (1129).…”