Research Article
Genotoxicity of11Heavy Metals Detected as Food
Contaminants in Two Human Cell Lines
B. Kopp,
1,2
D. Zalko,
1
and M. Audebert
1
*
1
Toxalim, Universit
e de Toulouse, INRA, INP-ENVT, INP-EI-Purpan,
Universit
e de Toulouse 3 Paul Sabatier, Toulouse, France
2
Toxicology of Contaminants Unit, French Agency for Food, Environmental and
Occupational Health & Safety, Fouge
`
res, France
Heavy metals, such as arsenic (As), antimony (Sb),
barium (Ba), cadmium (Cd), cobalt (Co), germanium
(Ge), lead (Pb), nickel (Ni), tellurium (Te), and vana-
dium (V) are widely distributed in the environment
and in the food chain. Human exposure to heavy met-
als through water and food has been reported by dif-
ferent international agencies. Although some of these
heavy metals are essential elements for human growth
and development, they may also be toxic at low con-
centrations 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 (gH2AX
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
2
> CdCl
2
> PbCl
2
(only in
LS-174T cells) > As
2
O
5
> SbCl
3
> K
2
TeO
3
> As
2
O
3
.
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 mMinboth
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.
V
C
2017 Wiley Periodicals, Inc.
Key words: genotoxicity; heavy metals; H2AX; human cells
INTRODUCTION
Heavy metals are naturally present in the environment,
in geologic parent material and rock outcroppings
[Tchounwou et al., 2012]. Since the industrial revolution,
readily available heavy metals have increased, often
reaching values that are toxic for a living organism [Silva
et al., 2017]. The main sources of heavy metals are agri-
cultural, followed by industrial activities, such as mining
and smelting. The term “heavy metals” is a generic term,
covering any metallic element (metals and metalloids)
that is stable and has a relatively high density compared
to water. Although heavy metals are considered as trace
elements in a number of environmental matrices, their
physical chemical properties (oxidation state, charge, and
ionic radii, geometry and type of ligands, solubility) influ-
ence their mobility and bioavailability, giving them a
high level of reactivity with biological systems. Some
heavy metals are vital for living organisms. They have
important biochemical and physiological functions, as
constituents of several key enzymes, and are co-factors
for many oxidation–reduction reactions [WHO, 1996].
Due to increasing levels of contamination in the environ-
ment, heavy metals can be present as residues in food,
either because raw plant/animal materials are contaminated,
or as secondary food contamination during industrial proc-
essing and storage. Thus, consumers may be exposed to dif-
ferent heavy metals by ingesting contaminated food or
water [EFSA, 2011]. The French Agency for Food, Envi-
ronmental and Occupational Health and Safety (ANSES)
confirmed this point in its second total diet study (TDS)
published in 2011 [ANSES, 2011]. The goal of the TDS
study was to gain a better understanding of human dietary
exposure to different food contaminants. It has been
*Correspondence to: Marc Audebert, PhD, INRA-UMR1331, Toxalim,
180 chemin de Tournefeuille BP 93173, 31027 Toulouse Cedex 3,
France. E-mail: marc.audebert@inra.fr
Received 28 July 2017; provisionally accepted 20 October 2017; and in
final form 23 October 2017
DOI 10.1002/em.22157
Published online 18 November 2017 in
Wiley Online Library (wileyonlinelibrary.com).
V
C
2017 Wiley Periodicals, Inc.
Environmental and Molecular Mutagenesis 59:202^210 (2018)
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