Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines

Abstract

Heavy metals, such as arsenic (As), antimony (Sb), barium (Ba), cadmium (Cd), cobalt (Co), germanium (Ge), lead (Pb), nickel (Ni), tellurium (Te), and vanadium (V) are widely distributed in the environment and in the food chain. Human exposure to heavy metals through water and food has been reported by different international agencies. Although some of these heavy metals are essential elements for human growth and development, they may also be toxic at low concentrations due to indirect mechanisms. In this study, the genotoxic and cytotoxic properties of 15 different oxidation statuses of 11 different heavy metals were investigated using high-throughput screening (γH2AX assay) in two human cell lines (HepG2 and LS-174T) representative of target organs (liver and colon) for food contaminants. Base on their lowest observed adverse effect concentration, the genotoxic potency of each heavy metal in each cell line was ranked in decreasing order, NaAsO > CdCl > PbCl (only in LS-174T cells) > As O > SbCl > K TeO > As O . No significant genotoxicity was observed with the other heavy metals tested. Cell viability data indicate that several heavy metals (As, Cd, Co, Ni, Sb, and Te) induce cytotoxicity at high concentrations, whereas an increase in the number of cells was observed for lead concentrations >100 µM in both cell lines tested, suggesting that lead stimulates cell growth. All these results highlight the possible human health hazards associated with the presence of heavy metals present in food. Environ. Mol. Mutagen. 59:202-210, 2018. © 2017 Wiley Periodicals, Inc.

Genotoxicity and mutagenicity assessment of food contaminant mixtures present in the French diet

“…The genotoxicity of this pesticide has previously been reported in a study using the comet assay (Vigreux et al, ) and its carcinogenicity may be linked to the formation of a specific metabolite and DNA adducts (Rakitsky et al, ). According to our previous report (Kopp et al, ), among the 11 metalloids tested, the rank of genotoxic potency in the two cell lines is as follows: NaAsO 2 > CdCl 2 > PbCl 2 (only in LS‐174 T cells) > SbCl 3 > K 2 TeO 3 . This is also fully consistent with the results of several studies focused on the genotoxic effects of these metalloids (Rudel et al, ; Takahashi et al, ; Beyersmann and Hartwig, ; Skipper et al, ).…”

“…The γH2AX biomarker can reveal a genotoxic insult resulting from diverse DNA damage, notably DNA adducts and oxidative DNA lesions (Watters et al, ; Smart et al, ; Khoury et al, ; Bryce et al, ; Khoury et al, ; Khoury et al, ; Bryce et al, ; Bryce et al, ). A wide range of genotoxic xenobiotics and food contaminants have previously been shown to induce γH2AX in vitro (Audebert et al, ; ; Graillot et al, ,b; Kopp et al, ).…”

“…PAHs are known to form bulky DNA adducts following metabolic bioactivation (Audebert et al, ; Xue and Warshawsky, ). Heavy metals can induce oxidative stress, inhibition of DNA repair systems and deregulation of cell proliferation (Beyersmann and Hartwig, ; Kopp et al, ; Simmons et al, ; Tchounwou et al, ). Some of the pesticides present in these mixtures have been shown to be genotoxic, although little information is available regarding the MOA of many of them (Bolognesi and Morasso, ; Graillot et al, ; ).…”

“…The phosphorylation of histone H2AX (named γH2AX) by different type of DNA lesions notably including DNA adducts, DNA abasic sites, DNA strand breaks or DNA replication or transcription blocking lesions, has been demonstrated in different studies with model genotoxicants (Watters et al, ; Smart et al, ; Khoury et al, ; Bryce et al, ; ; ; Khoury et al, ,b). The in vitro γH2AX in‐cell Western (ICW) assay has been successfully used to simultaneously analyze the DNA damage and cytotoxicity (relative cell count) potential of different food contaminants (Audebert et al, ; Graillot et al, ; Theumer et al, ; Kopp et al, ), including mixtures of pesticides (Graillot et al, ). Of the 49 chemicals, 21 were tested specifically for this study whereas the other 28 had already been published (supplementary data 4).…”

Novel strategies for risk assessment of pyrrolizidine alkaloids

“…The γH2AX ICW assay was used to quantify the genotoxicity of these PAs in primary rat hepatocytes. So far, the γH2AX ICW assay has been successfully applied to evaluate the genotoxiciy of several food contaminants, including aflatoxins (Theumer et al, 2018), heavy metals (Kopp et al 2018), polycyclic aromatic hydrocarbons (Audebert et al, 2010;Audebert et al, 2012) and PAs (Louisse et al, Submitted), for possible genotoxicity.…”