Genotoxic impact of aluminum-containing nanomaterials in human intestinal and hepatic cells

Pégah Jalili,Sylvie Huet,Agnès Burel,Benjamin-Christoph Krause,Caroline Fontana,Soizic Chevance,Fabienne Gauffre,Yves Guichard,Alfonso Lampen,Peter Laux,Andreas Luch,Kevin Hogeveen,Valérie Fessard

doi:10.1016/j.tiv.2021.105257

Abstract

Exposure of consumers to aluminum-containing nanomaterials (Al NMs) is an area of concern for public health agencies. As the available data on the genotoxicity of Al2O3 and Al0 NMs are inconclusive or rare, the present study investigated their in vitro genotoxic potential in intestinal and liver cell models, and compared with the ionic form AlCl3. Intestinal Caco-2 and hepatic HepaRG cells were exposed to Al0 and Al2O3 NMs (0.03 to 80 μg/cm2). Cytotoxicity, oxidative stress and apoptosis were measured using High Content Analysis. Genotoxicity was investigated through γH2AX labelling, the alkaline comet and micronucleus assays. Moreover, oxidative DNA damage and carcinogenic properties were assessed using the Fpg-modified comet assay and the cell transforming assay in Bhas 42 cells respectively.The three forms of Al did not induce chromosomal damage. However, although no production of oxidative stress was detected, Al2O3 NMs induced oxidative DNA damage in Caco-2 cells but not likely related to ion release in the cell media. Considerable DNA damage was observed with Al0 NMs in both cell lines in the comet assay, likely due to interference with these NMs. No genotoxic effects were observed with AlCl3. None of the Al compounds induced cytotoxicity, apoptosis, γH2AX or cell transformation.

Highlights

Within the last decade, aluminum (Al)-containing nanomaterials (NMs) have been widely used for industrial applications, and in consumer products, due to their higher reactivity compared to the bulk form [1, 2, 3, 4]
The slight effects observed with aluminum-containing nanomaterials (Al NMs) are not likely to be related to ion release in the cell media
In contrast to the information provided by the suppliers, the particle morphology of Al2O3 NMs in the stock dispersion solution cannot be considered as being spherical, but rather have a rod-like shape when observed by transmission electron microscopy (TEM) (Figure S1)

Summary

Introduction

Aluminum (Al)-containing nanomaterials (NMs) have been widely used for industrial applications, and in consumer products, due to their higher reactivity compared to the bulk form [1, 2, 3, 4]. Forms of Al, both in the micro-and the nano-size, are present in food and consumer products [1, 5] due to their use as firming, anticaking, neutralizing, emulsifying and texturizing agents, as well as for cooking tools [6], waste water treatment [7, 8] and in medical and hygiene products such as toothpaste [9, 10, 11] Their potential toxicity has not been fully evaluated, leading to major concerns from consumers and public health agencies [12]. 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

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