Effect of age on acute toxicity of cadmium, copper, nickel, and zinc in individual-metal exposures to Daphnia magna neonates.
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ABSTRACT:
SUBMITTER: Traudt EM
PROVIDER: S-EPMC5764767 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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Effect of age on acute toxicity of cadmium, copper, nickel, and zinc in individual-metal exposures to Daphnia magna neonates.
Traudt Elizabeth M EM Ranville James F JF Meyer Joseph S JS
Environmental toxicology and chemistry 20160721 1
In previous studies, variability was high among replicate acute cadmium (Cd) Daphnia magna lethality tests (e.g., >10-fold range of median effect concentrations [EC50s]), less among zinc (Zn) tests, and relatively low for copper (Cu) and nickel (Ni) tests. Although the US Environmental Protection Agency's (USEPA's) protocol includes starting toxicity tests with neonates less than 24 h old, the authors hypothesized that age-related differences in sensitivity to metals might occur even within that ...[more]
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Project description:Background: Toxicogenomics provides new opportunities for innovative and proactive approaches to chemical screening, risk assessment, and predictive toxicology. If applied to ecotoxicology, genomics tools could greatly enhance the ability to detect toxicants and understand the modes of toxicity in an environmental setting. However, few studies have yet to illustrate the potential of genomic techniques in ecotoxicology. Objective: Therefore, our objective was to demonstrate the potential utility of gene expression profiling in ecotoxicology using Daphnia magna, a standard aquatic ecotoxicity test organism. Methods: D. magna were exposed to copper, cadmium, and zinc at the 1/10 LC50 for 24 hours. Following each exposure, RNA was isolated, reverse transcribed, and the cDNA was hybridized to a 5000 clone cDNA microarray for D. magna. Differentially expressed cDNAs were sequenced and homology searches revealed each gene product's potential function. Real time PCR was used to verify the differential expression of several genes, and enzyme assays were used to assess the significance of these changes. Results: We identified distinct expression profiles in response to acute copper, cadmium, and zinc exposures and discovered specific biomarkers of exposure including two probable metallothioneins, and a ferritin mRNA with a functional IRE. The gene expression patterns support known mechanisms of metal toxicity and reveal novel modes of action including zinc inhibition of chitinase activity. Conclusions: Using a cDNA microarray for traditional ecotoxicology organism, D. magna, we have identified novel biomarkers of exposure and revealed possible modes of toxicity, providing experimental support for the utility of ecotoxicogenomics. Keywords: comparative toxicant exposure
2006-12-22 | GSE4759 | GEO
Project description:The recent development of a custom cDNA microarray platform for one of thé standard organisms in aquatic toxicology, Daphnia magna, opened up new ways to mechanistic insights of toxicological responses. In this study, gene expression and (sub)organismal responses (Cellular Energy Allocation, growth) were assayed after short-term waterborne metal exposure. Microarray analysis of Ni-exposed daphnids revealed several affected functional gene classes, of which the largest ones were involved in different metabolic processes (mainly protein and chitin related processes), cuticula turnover, transport and signal transduction. Furthermore, genes involved in oxygen transport and heme metabolism (hemoglobin, δ-aminolevilunate synthase) were down-regulated. Applying a Partial Least Squares regression on nickel fingerprints and biochemical (sub)organismal parameters revealed a set of co-varying genes (hemoglobin, RNA terminal phosphate cyclase, a ribosomal protein and an “unknown” gene fragment). An inverse relationship was seen between the mRNA expression levels of different cuticula proteins and available energy reserves. In addition to the nickel exposure, daphnids were exposed to binary mixtures of nickel and cadmium or nickel and lead. Using multivariate analysis techniques, the mixture gene expression fingerprints (Ni2++Cd2+, Ni2++Pb2+) were compared to those of the single metal treatments (Ni2+, Cd2+, Pb2+). It was hypothesized that the molecular fingerprints of the mixtures would be additive combinations of the gene expression profiles of the individual compounds present in the mixture. However, our results clearly showed additionally affected pathways after mixture treatment (e.g. additional affected genes involved in carbohydrate catabolic processes and proteolysis), indicating interactive molecular responses which are not merely the additive sum of the individual metals. These findings, although indicative of the complex nature of mixture toxicity evaluation, underline the potential of a toxicogenomics approach in gaining more mechanistic information on the effects of single compounds and mixtures.
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Project description:The use of anticancer drugs in chemotherapy is increasing, leading to growing environmental concentrations of imatinib mesylate (IMA), cisplatinum (CDDP), and etoposide (ETP) in aquatic systems. Previous studies have shown that these anticancer drugs cause DNA damage in the crustacean Daphnia magna at low, environmentally relevant concentrations. To explore the mechanism of action of these compounds and the downstream effects of DNA damage on D. magna growth and development at a sensitive life stage, we exposed neonates to low level concentrations equivalent to those that elicit DNA damage (IMA: 2000 ng/L, ETP: 300 ng/L, CDDP: 10 ng/L) and performed transcriptomic analysis using an RNA-seq approach. RNA sequencing generated 14 million reads per sample, which were aligned to the D. magna genome and assembled, producing approximately 23,000 transcripts per sample. Over 90% of the transcripts showed homology to proteins in GenBank, revealing a high quality transcriptome assembly, although functional annotation was much lower. RT-qPCR was used to identify robust biomarkers and confirmed the downregulation of angiotensin converting enzyme (ACE) involved in neuropeptide regulation across all three anticancer drugs and the down-regulation of DNA topoisomerase II by ETP. RNA-seq analysis also allowed for an in depth exploration of the differential splicing of transcripts revealing that regulation of different gene isoforms predicts potential impacts on translation and protein expression, providing a more meaningful assessment of transcriptomic data. Enrichment analysis and investigation of affected biological processes suggested that the DNA damage caused by ETP and IMA influences cell cycle regulation and GPCR signaling. This dysregulation is likely responsible for effects to neurological system processes and development, and overall growth and development. Our transcriptomic approach provided insight into the mechanisms that respond to DNA damage caused by anticancer drug exposure and generated novel hypotheses on how these chemicals may impact the growth and survival of this ecologically important zooplankton species.
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2010-05-22 | E-GEOD-13866 | biostudies-arrayexpress
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