title: Transcriptional responses indicate attenuated oxidative stress in the springtail Folsomia candida exposed to mixtures of cadmium and phenanthrene.
abstract: Since the 'omics revolution', the assessment of toxic chemical mixtures has incorporated approaches where phenotypic endpoints are connected to a mechanistic understanding of toxicity. In this study we determined the effect of binary mixtures of cadmium and phenanthrene on the reproduction of Folsomia candida and investigated the cellular mechanisms underlying this response. Mixture toxicity modeling showed an antagonistic deviation from concentration addition for reproduction effects of the mixtures. Subsequent transcriptional response analysis was done using five mixtures at the modeled 50 % effect level for reproduction. The transcription profiles of 86 high throughput RT-qPCR assays were studied by means of partial least squares regression analysis. The first and second principal components (PCs) were correlated with global responses to cadmium and phenanthrene, while correlations with the mixture treatments were found in the higher PCs. Specifically associated with the mixture treatments were a biotransformation phase II gene, four mitochondrial related genes and a gene involved in the biosynthesis of antioxidant selenoproteins. Membrane integrity related gene inductions were correlated with the single phenanthrene treatment but not with the mixtures. Immune and inflammatory response assays did not correlate with any of the mixtures. These results suggest moderated oxidative stress, a higher mitochondrial maintenance and less compromised membrane function in the mixture exposed samples compared to the separate cadmium or phenanthrene exposures. The antagonism found for inhibition of reproduction may partially originate from these differences. Mechanistic studies on mixture toxicity can ultimately aid risk assessment by defining relevant toxicity pathways in organisms exposed to real-world mixture exposures present in the field.
authors.affiliation: Department of Ecological Science, VU University Amsterdam, De Boelelaan 1085, Amsterdam, 1081, HV, The Netherlands, muriel.de.boer@gmail.com
authors.forename: Muriel E
authors.initials: ME
authors.lastname: de Boer
authors.forename: Jacintha
authors.initials: J
authors.lastname: Ellers
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: van Gestel
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
authors.forename: Nico M
authors.initials: NM
authors.lastname: van Straalen
authors.forename: Dick
authors.initials: D
authors.lastname: Roelofs
mesh_terms: D000818:Animals; D001181:Arthropods / Q000187:drug effects*; D001711:Biotransformation; D002104:Cadmium / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015999:Multivariate Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D010616:Phenanthrenes / Q000633:toxicity*; D012313:RNA / Q000235:genetics; D012098:Reproduction / Q000187:drug effects; D059467:Transcriptome
chemical_list: D010616:Phenanthrenes; D002104:Cadmium; C031181:phenanthrene; D012313:RNA; D003577:Cytochrome P-450 Enzyme System