Genotoxic Impact of Aluminum-containing Nanomaterials in Human Intestinal and Hepatic Cells.

Abstract

Background: Exposure of consumers to aluminum-containing nanomaterials (Al NMs) through numerous products is an area of concern for public health agencies since human health risks are not completely elucidated. In addition, the available data on the genotoxicity of Al2O3 and Al0 NMs are inconclusive or rare. In order to provide further information, the present study investigated the in vitro genotoxic potential of Al0 and Al2O3 NMs in intestinal and liver cell models since these tissues represent organs which would be in direct contact or could experience potential accumulation following oral exposure. Methods: Differentiated human intestinal Caco-2 and hepatic HepaRG cells were exposed to Al0 and Al2O3 NMs (0.03 to 80 µg/cm2) and the results were compared with those obtained with the ionic form AlCl3. Several methods, including H2AX labelling, the alkaline comet assay and micronucleus (MN) assays were used. Oxidative stress and oxidative DNA damage were assessed using High Content Analysis (HCA) and the formamidopyrimidine DNA-glycosylase -modified comet assay respectively. Moreover, carcinogenic properties of Al NMs were investigated through the cell transforming assay (CTA) in Bhas 42 cells.Results: The three forms of Al did not induce chromosomal damage when tested in the MN assay. Furthermore, no cell transformation was observed in Bhas 42 cells. However, although no production of oxidative stress was detected in HCA assays, Al2O3 NMs induced oxidative DNA damage in Caco-2 cells in the comet assay following a 24 h treatment. Considerable DNA damage was observed with Al0 NMs in both cell lines in the comet assay, although this was likely due to interference with these NMs. Finally, no genotoxic effects were observed with AlCl3. Conclusion: The slight effects observed with Al NMs are therefore not likely to be related to ion release in the cell media.

The miniaturized enzyme-modified comet assay for genotoxicity testing of nanomaterials

“…Most conventional toxicity assays rely on colorimetric/fluorometric principals, and the particular physical properties of NMs mean that they are prone to interfere with testing methods, as shown in several studies (Ong et al, 2014). Possible interference between NMs and the comet assay has been investigated (Kain et al, 2012;Magdolenova et al, 2012;Karlsson et al, 2015;Ferraro et al, 2016;George et al, 2017;Jalili et al, 2022). For instance, Ferraro et al, 2016, showed a possible interaction between naked DNA and NMs just before the electrophoresis step (Ferraro et al, 2016).…”