RESEARCH ARTICLE
Toxicity interactions between manganese (Mn) and lead (Pb)
or cadmium (Cd) in a model organism the nematode C. elegans
Cailing Lu
1,2
&
Kurt R. Svoboda
1
&
Kade A. Lenz
1
&
Claire Pattison
1
&
Hongbo Ma
1
Received: 1 December 2017 / Accepted: 13 March 2018 / Published online: 21 March 2018
#
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract
Manganese (Mn) is considered as an emerging metal contaminant in the environment. However, its potential interactions with
companying toxic metals and the associated mixture effects are largely unknown. Here, we investigated the toxicity interactions
between Mn and two commonly seen co-occurring toxic metals, Pb and Cd, in a model organism the nematode Caenorhabditis
elegans. The acute lethal toxicity of mixtures of Mn+Pb and Mn+Cd were first assessed using a toxic unit model. Multiple
toxicity endpoints including reproduction, lifespan, stress response, and neurotoxicity were then examined to evaluate the
mixture effects at sublethal concentrations. Stress response was assessed using a daf-16::GFP transgenic strain that expresses
GFP under the control of DAF-16 promotor. Neurotoxicity was assessed using a dat-1::GFP transgenic strain that expresses GFP
in dopaminergic neurons. The mixture of Mn+Pb induced a more-than-additive (synergistic) lethal toxicity in the worm whereas
the mixture of Mn+Cd induced a less-than-additive (antagonistic) toxicity. Mixture effects on sublethal toxicity showed more
complex patterns and were dependent on the toxicity endpoints as well as the modes of toxic action of the metals. The mixture of
Mn+Pb induced additive effects on both reproduction and lifespan, whereas the mixture of Mn+Cd induced additive effects on
lifespan but not reproduction. Both mixtures seemed to induce additive effects on stress response and neurotoxicity, although a
quantitative assessment was not possible due to the single concentrations used in mixture tests. Our findings demonstrate the
complexity of metal interactions and the associated mixture effects. Assessment of metal mixture toxicity should take into
consideration the unique property of individual metals, their potential toxicity mechanisms, and the toxicity endpoints examined.
Keywords Manganese
.
Cadmium
.
Lead
.
Toxicity interaction
.
Metal mixture
.
C. elegans
Introduction
Manganese (Mn) is one of the most abundant and broadly
distributed metals in nature, and the massive production and
application of Mn-containing compounds has led their release/
disposal to the environment. As an essential metal, Mn plays
important roles in many biological and physiological process-
es. However, exposure to excessive amounts of Mn can cause
toxicological effects in humans and environmental organisms.
In humans, Mn excess induces neurotoxicity associated with a
BParkinson-like^ syndrome called Bmanganism^, character-
ized by rigidity, action tremor, memory and cognitive dys-
function, and micrograph and mood disorder (Cersosimo
and Koller 2006). Occupational manganism is estimated to
be 0.5–2% among exposed welding workers in southwest
China (Gao et al. 2003; Wang 2003), where metal poisoning
ranks among the top 10 leading occupational hazards (Liang
and Xiang 2004). In the USA, the cost of legal litigation re-
lating to occupational Mn-related disorders is estimated to be
in billions of dollars (Times 2003). More recent studies in the
past decade suggest that low-level occupational exposure with
Mn concentrations below occupational standards can also be
detrimental to human health, inducing neurochemical and
neurobehavioral changes that are linked to pathogenic condi-
tions (O’Neal and Zheng 2015). For the general public, ele-
vated Mn exposure can occur through contaminated air,
groundwater, and food and lead to adverse health effects.
High levels of Mn in drinking water have been linked to
Responsible editor: Philippe Garrigues
* Hongbo Ma
hongboma@uwm.edu
1
Joseph J. Zilber School of Public Health, University of
Wisconsin-Milwaukee, 1240 N 10th St, Milwaukee, WI, USA
2
School of Public Health, Guangxi Medical University, 22
Shuangyong Rd, Nanning, Guangxi, China
Environmental Science and Pollution Research (2018) 25:15378–15389
https://doi.org/10.1007/s11356-018-1752-5
@Phil_Robichaud
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