The interplay between chemical speciation and physiology determines the bioaccumulation and toxicity of Cu(II) and Cd(II) to Caenorhabditis elegans

Abstract

Using the well-documented model organism Caenorhabditis elegans, a combined analysis of metal speciation in the exposure medium and body burdens of metals (Zn, Cu and Cd) was performed, and factors that are predictive of toxicological endpoints in single metal and mixed metal exposures were identified. Cu, and to a lesser extent Cd, is found to associate with Escherichia coli in the exposure medium (the food source for C. elegans) as evidenced by the observed decrease in both their dissolved and free metal ion concentrations. Together with a critical analysis of literature data, our results suggest that free metal ion concentrations and thus aqueous uptake routes are the best predictor of internal concentrations under all conditions considered, and of metal toxicity in single metal exposures. Additional factors are involved in determining the toxicity of metal mixtures. In general, the eventual adverse effects of metals on biota are expected to be a consequence of the interplay between chemical speciation in the exposure medium, timescale of exposure, exposure route as well as the nature and timescale of the biotic handling pathways.

Strength of Cu-efflux response in Escherichia coli coordinates metal resistance in Caenorhabditis elegans and contributes to the severity of environmental toxicity

“…Next, we tested whether reduced bacterial Cu-efflux capacity improved the aforementioned C. elegans Cu-toxicity endpoints by reducing the overall quantity, or internal dose, of Cu in C. elegans following the same 48 h exposure to 100 μM Cu since increases in measured Cu-body burden are consistent indicators of excess metal concentration in the environment and are predictive of dose-dependent toxicity ( 40 ). To quantify the C. elegans Cu-body burden, nematodes were collected after the limited 48 h exposure ( Fig.…”

“…The removal or silencing of Cu-homeostatic elements reduces Cu-body burden in nematodes while increasing the severity of Cu-toxicity endpoints at higher concentration of environmental Cu (31,32). Without genetic silencing of Cu homeostatic elements in nematodes, the free water-borne fraction of Cu in the environment was shown J o u r n a l P r e -p r o o f to be the most significant contributor to the Cu-body burden and subsequent toxicity in conditions of Cu excess (33,40). While the potential role for bacterially-associated Cu is recognized, the impact was considered minimally additive to the body-burden and toxicity of free water-borne exposures (35,38).…”

“…Evidence for conserved Cu-homeostatic elements is found in orthologs for a passive Cu-uptake transporter ( 31 ) and the active Cu exporter ATP7A/B ( 32 ), which are both expressed along the nematode’s digestive tract, mirroring the expression patterns and physiology of higher organisms ( 14 , 20 ). Under Cu stress, nematodes also present dose-dependent Cu-toxicity responses that encompass developmental, behavioral, reproductive, and aging trajectories, which may be influenced by bacterial activity ( 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ). Furthermore, these responses to metal stress are often consistent and conserved across species, allowing for a detailed investigation of host stress responses mediated by bacterial activity.…”

Recombinant human metallothionein‐III alleviates oxidative damage induced by copper and cadmium in Caenorhabditis elegans

“…Considering that the accumulation effects of heavy metals will aggravate the exposure doses and harm of metals in the organisms, we combined the nematode model and further searched for the LC50 exposure experiments of the Cu 2+ and Cd 2+ to C. elegans in the literatures at home and abroad. It was found that the growth and metabolism were significantly inhibited when both metal exposures reached 10 μg/mL and stimulated oxidative stress and lipid peroxidation occurred (Moyson et al, 2019). Therefore, 10 μg/mL was selected as the exposure dose for Cu 2+ /Cd 2+ to induce nematode damage in this study.…”

Arabidopsis root growth and development under metal exposure presented in an adverse outcome pathway framework

“…Risk assessments, even by modern legislations such as Regulation for Registration, Evaluation, Authorization and Restriction of Chemicals (REACH), are usually performed on single metal exposure and thus fully ignore the mixture effects (Backhaus & Faust, 2012 ). Furthermore, it is well established that the combination of different chemicals can produce significant toxic effects, even though they may cause no or very limited observable effects when applied individually (Moyson, Town, Joosen, Husson, & Blust, 2019 ). There is thus a need to understand how metals act together in mixtures and how these should be handled in a regulatory risk assessment context (Backhaus & Faust, 2012 ).…”