Contents lists available at ScienceDirect Comparative Biochemistry and Physiology, Part C journal homepage: www.elsevier.com/locate/cbpc Gene expression changes and toxicity of selected rare earth elements in rainbow trout juveniles M. Dubé, J. Auclair, H. Hanana, P. Turcotte, C. Gagnon, F. Gagné ⁎ Aquatic Contaminants Research Division, Environment and Climate Change Canada, 105 McGill, Montréal H2Y 2E7, Québec, Canada ARTICLE INFO Keywords: Rare earth elements Fish Mortality Gene expression ABSTRACT Rare earth elements (REEs) are increasingly used in electronics industry and other areas of our economy and questions were raised about their impacts to the environment. The purpose of this study was to examine the lethal and sublethal toxicity of REEs in juvenile rainbow (Oncorhynchus mykiss) trout. The fish were exposed to increasing concentrations (0.064, 0.32, 1.6, 8 and 40 mg/L) of the following 7 REEs for 96 h at 15 °C: cerium (CeCl 3 ), erbium (ErCl 3 ), gadolinium (GdCl 3 ), lanthanum (LaCl 3 ), neodymium (NdCl 3 ), samarium (SmCl 3 ) and yttrium (YCl 3 ). The mortality were determined and in the surviving fish, 10 target gene transcripts were mea- sured in the liver to track changes in oxidative stress, DNA repair, tissue growth/proliferation, protein cha- peroning, xenobiotic biotransformation and ammonia metabolism. The data revealed that Y, Sm, Er and Gd formed a distinct group based on toxicity (mortality) and gene expression changes. Electronegativity was sig- nificantly correlated (r = -0.8, p < 0.01) with the lethal concentration (LC50). Gene expression changes oc- curred at concentration circa 120 times lower than the LC50 and the following transcripts in protein chaperoning (heat shock proteins), DNA repair (growth arrest DNA Damage) and CYP1A1 gene expression involved in the metabolism of coplanar aromatic hydrocarbons were involved. In conclusion, the study revealed that the more electronegative REEs were the most toxic to trout juveniles and produced sublethal effects at concentrations 2 orders of magnitude lower than the lethal concentrations. The toxicity of REEs depends on the elements were toxicity involves specific pathways at the gene expression level. 1. Introduction Rare earth elements (REEs) consist of a group of 15 elements composed of the lanthanides family (z = 57 to 71) with yttrium (Y, z = 39) and scandium (Sc, z = 21). Initially, the properties of lantha- nides are considered similar closely mirroring that of lanthanum (La) while differing on other aspects such as molecular weight, ionic radius and electronegativity. These elements are used in various area of our technology such as medicine, electronic device (cell phones, plasma screens), and permanent magnets. Hence, the increased mining of REEs and processing into commercial products have exponentially grown over the past years and raised environmental concerns about their in- advertent release in aquatic and terrestrial ecosystems. For example, increased concentration in REEs have been reported in lakes (Sheard et al., 2012), sediments (Oliveira et al., 2007) and in the urban atmo- sphere (Moreno et al., 2010). The aquatic toxicity and mode of action of lanthanides have been examined in a recent review (Gonzalez et al., 2014). Moreover, most toxicity studies aimed at understanding on the mechanisms at play focused mostly on La which is considered a representative REEs al- though the toxic properties might not be uniformly distributed across this group of elements as initially anticipated. For example, gadolinium (Gd) and praseodymium (Pr) decrease cytochrome P450 activity in hepatocytes thus protecting against products of xenobiotic bio- transformation while dysprosium (Dy) and La blocks Ca 2+ /Mg 2+ AT- Pase (Pałasz and Czekaj, 2000). This is keeping with the variable toxicity of REEs observed towards aquatic organisms such as the Hydra (Blaise et al., 2018) and some fish species (Gonzalez et al., 2014). In a recent review, the adverse effects of REEs differed depending on the elements where the authors also found that the toxicological database was mainly confined to cerium (Ce) and La (Pagano et al., 2015). Ac- cording to this review, adverse effects were reported with Sc, Y, La, Ce, Pr, Gd and Nd based on published data. REEs seems to alter the redox homeostasis in a peculiar manner (hormesis response) producing sometimes antioxidant effects at low concentration and oxidative stress at higher concentrations. For example, Ce and Y oxide nanoparticles were shown to decrease oxidative stress and protect nerve tissues against injury (Schubert et al., 2006) and Ce increased reduced https://doi.org/10.1016/j.cbpc.2019.05.009 Received 8 March 2019; Received in revised form 8 May 2019; Accepted 10 May 2019 ⁎ Corresponding author. E-mail address: francois.gagne@canada.ca (F. Gagné). Comparative Biochemistry and Physiology, Part C 223 (2019) 88–95 Available online 31 May 2019 1532-0456/ © 2019 Published by Elsevier Inc. T