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

Abstract

Through diet, people are exposed simultaneously to a variety of contaminants (e.g. heavy metals, mycotoxins, pesticides) that could have combined adverse effects on human health. A previous study identified six main mixtures of food contaminants to which French adult consumers are exposed. These complex mixtures are comprised of 11 to 19 chemicals that have numerous toxic properties. In the present study, we investigated the genotoxic effects of these food contaminants, as single molecules and in mixtures that reflect their occurrence in the French diet, using the γH2AX assay in two human cell lines (HepG2, LS-174 T). Results of detailed analysis of the 49 individual contaminants (including 21 tested in this study) demonstrated a positive genotoxic response to 14 contaminants in HepG2 and 12 in LS-174 T cells. Next, our results indicated that two mixtures out of six triggered significant γH2AX induction after 24 hr of treatment, at concentrations for which individual compounds did not induce any DNA damage, suggesting more than additive interactions between chemicals. γH2AX positive mixtures were then tested for mutagenicity with the innovative in vitro PIG-A assay in HepG2 cells coupled with the soft agar colony formation assay. The two γH2AX positive mixtures led to a significant increase in the frequency of PIG-A GPI-deficient cells and in the number of colonies formed in soft agar. In conclusion, our study demonstrates that two mixtures of contaminants present in the French diet induce genotoxicity and mutagenicity, and that the combined effects of single molecules present in these mixtures are likely not additive, highlighting potential problems for hazard assessment of mixtures. Environ. Mol. Mutagen. 59:742-754, 2018. © 2018 Wiley Periodicals, Inc.

Synergic toxic effects of food contaminant mixtures in human cells

“…In a previous work, we observed that two mixtures of food contaminants present in the French diet were genotoxic and mutagenic in HepG2 and HepaRG cells (26,27). Furthermore, the genotoxic and cytotoxic effects observed with these two mixtures, suggested some degree of interaction between the compounds.…”

“…Depending on their solubility, compounds were dissolve either in pure water (EMD Millipore) or in dimethyl sulfoxide (DMSO) as previously described. As detailed in our previous papers (26,27), depending on their solubility, each compound was first dissolved either in pure water or in DMSO, hereafter referred to the "DMSO phase" and the "water phase". DMSO-phase contained uniquely the organic compounds and water-phase contained uniquely heavy metals.…”

“…In vitro mutagenicity study with the PIG-A assay. In vitro mutagenicity was investigated with the PIG-A assay as previously described (27). Mutant frequencies was calculate as the number of GPI (-) cells divided by the number of total living cells analyzed and expressed as a fold change.…”

Effets des polluants environnementaux et alimentaires sur le microbiote intestinal

“…Chaque mélange identifié comprend de 11 à 19 composés toxiques dont les métaux lourds, les hydrocarbures aromatiques polycycliques, les mycotoxines, les pesticides et d'autres xénobiotiques (bisphénol A, acrylamide, acide perfluorooctanoïque). La toxicité de ces composés seuls ou en mélange a été démontrée sur des cellules de foie et de côlon [21]. L'exposition à ces composés toxiques a également été mise en évidence chez les femmes enceintes en France avec les dernières études nationales EDEN : « Etude sur les déterminants pré-et post-natals précoces du développement psychomoteur et de la santé de l'enfant » et ELFE : « Etude longitudinale française depuis l'enfance » en lien avec la deuxième étude de l'alimentation totale française EAT2 [22].…”

Analysis of Chromosomal Damage Caused by Acetamiprid

“…Intensive use of pesticides leads to environmental contamination. It directly affects the soil, water flows, groundwater, non-target organisms, and last but not least, can affect the animal and human health by careless and improper use [7]. In livestock, there is a decline in performance and consequently, high economic losses for breeders.…”