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Transcriptomic response of zebrafish embryos to Polyamidoamine (PAMAM) dendrimers

ABSTRACT: We are presenting here the application of toxicogenomics to perform the evaluation of toxic effects of two polyamidoamine dendrimers (Generation3 and Generation4) on the developing zebrafish embryo. They are nanomaterials of special concern under the toxicological point of view because of their relatively high solubility in water and bioavailability. Zebrafish embryo toxicity assays (zFET) showed that G3 was more toxic to zebrafish than G4, and that both compounds were several orders of magnitude more toxic than other carbonaceous nanomaterials, like carbon fullerenes or nanotubes. The results suggest a variety of MoA for different dendrimers, probably related to the nature and number of the chemical groups attached to their surface. They also confirm the relatively high bioavailability of these compounds, a key factor for the assessment of the risk associated to their use and release into the environment. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process and also in the nervous system development. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of generations of dendrimers studied.

ORGANISM(S): Danio rerio

PROVIDER: GSE41333 | GEO | 2013/11/12

SECONDARY ACCESSION(S): PRJNA176662

REPOSITORIES: GEO

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Transcriptomic response of zebrafish embryos to Polyamidoamine (PAMAM) dendrimers

Project description:We are presenting here the application of toxicogenomics to perform the evaluation of toxic effects of two polyamidoamine dendrimers (Generation3 and Generation4) on the developing zebrafish embryo. They are nanomaterials of special concern under the toxicological point of view because of their relatively high solubility in water and bioavailability. Zebrafish embryo toxicity assays (zFET) showed that G3 was more toxic to zebrafish than G4, and that both compounds were several orders of magnitude more toxic than other carbonaceous nanomaterials, like carbon fullerenes or nanotubes. The results suggest a variety of MoA for different dendrimers, probably related to the nature and number of the chemical groups attached to their surface. They also confirm the relatively high bioavailability of these compounds, a key factor for the assessment of the risk associated to their use and release into the environment. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process and also in the nervous system development. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of generations of dendrimers studied. Two different treatments were performed in this study. Zebrafish fertlized eggs were exposed to PAMAM dendrimer G3 and G4 during 48h. 3 biological replicates per studied dendrimer are included such as each control sample.

2013-11-12 | E-GEOD-41333 | biostudies-arrayexpress

Transcriptomic analysis of dioxin like compounds

Project description:We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of three dioxin-like compounds, two Polycyclic aromatic hydrocarbons (PAHs), Benzo(a)pyrene, Benzo(k) fluoranthene and b-naphthoflavone on the developing zebrafish embryo. The main goal is to distinguish the pattern of action of the chemical compounds and their needs varying the times of exposure. The results suggest a variety of MoA for different dioxin-like compounds, probably related to the nature and number of benzene rings. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of dioxin-like compounds studied.

2015-12-31 | GSE41334 | GEO

Transcriptional responses to engineered nanoplatforms for drug delivery in primary human aortic endothelial cells.

2013-12-20 | GSE35142 | GEO

Transcriptional responses to engineered nanoplatforms for drug delivery in primary human aortic endothelial cells.

Project description:This study evaluated transcriptional effects of nanomaterials that have been proposed for use as platforms for drug delivery. We tested SiO2 that had been surface modified to have a positive zetapotential of different geometries as well PAMAM dendrimers with different surface charges. We tested these materials on human aortic endothelial cells (HAECs) since we were interested in determining if there was a toxicogenomic response in endothelial cells that may come into contact with drug delivery nanoplatforms. The most pronounced transcriptional response resulted from the SiO2 treatement - the most prevelant responses were cell cycle, lipid metabolism and pro-inflammatory responses - with fewer responses from the PAMAM dendrimers. The lipid metabolism responses may relate to teh positive surface character as this response was not observed in the G3.5-COOH dendrimers. Indeed, the G3.5-COOH dendrimers were non-toxic and did not demonstrate any consistent transcriptional response. Primary human aortic endothial cells (HAECs) were grown in 6 well plates (in 2 ml of medium) until they were >80% confluent by visual inspection. Daily media changes allowed continued growth for HAECs that demonstrate contact inhibition. The cells were then incubated with nanomaterials: surface modified SiO2 with worm and sphere goemetries (the spheres were 200 nm in diameter and the worm's cylindrical diameter 200 nm and the length was ~ 1000 nm); and PAMAM dendrimers with different surface charges (G3.5-COOH are negative and G4-NH2 are positive). RNA was collected after 4 and 24 hrs (one SiO2 worm sample was at 1.5 hrs due to space available on the 4-pack microarrays). Triplicate biological samples (indicated by the 'a', 'b', and 'c' designations in the sample names) were evaluated for gene expression changes by microarray analysis.

2013-12-20 | E-GEOD-35142 | biostudies-arrayexpress

Gene expression profiling in zebrafish embryos exposed to 3,4-dichloroaniline (3,4-DCA)

Project description:The zebrafish (Danio rerio) embryo toxicity test (DarT) is considered as an alternative to the acute fish toxicity test. However, DarT rarely reveals information on the mechanisms underlying a toxic effect and is relatively insensitive compared to chronic toxic effects. We hypothesized that, by using gene expression profiles as an additional endpoint, it may be possible to increase the sensitivity and predictive value of DarT. Therefore we exposed zebrafish embryos for 48 h to the reference compound 3,4-dichloroaniline and analyzed gene expression patterns with a 14 k oligonucleotide array. Keywords: differential gene expression upon chemical exposure in zebrafish embryos

2006-11-08 | GSE6228 | GEO

Transcriptomic analysis of Retinoic acid and 9 cis retinoic acid in zebrafish.

Project description:We are presenting the application of toxicogenomics in the evaluation of the toxic effects of retinoic acid and one of its isoforms the 9-cis retinoic acid. The main goal is to distinguish the pattern of action of the both chemical compounds and their action in an extended exposure. The results suggest a different pattern within the days and the chemicals. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of retinoic acid compounds studied.

2015-12-31 | GSE41335 | GEO

Identification of circular RNAs expression pattern in caprine fetal fibroblast cells exposed to a chronic noncytotoxic dose of graphene oxide-silver nanoparticle nanocomposites

Project description:circRNA sequencing for 6 samples.The increasing use of graphene oxide-silver nanoparticle nanocomposites (GO-AgNPs) in biomedical sciences and research also increases the chances of human and animal exposure to its chronic non-toxic doses. However, the available information is truly little for profound understanding of the effect of low-dose chronic exposure to GO-AgNPs on the epigenetic modification of the organism. In this research, we have investigated the impact of non-toxic doses of GO-AgNPs (0.5 µg/mL for 10 weeks, this dose does not interfere cell viability and ROS level) on the differential expression of circular RNAs (circRNAs) in caprine fetal fibroblast cells (CFFCs). In addition, using bioinformatics tools we have predicted the functions of those differentially expressed circRNAs on CFFCs. Furthermore, we have validated the expression of ten circRNAs using qRT-PCR to ensure the reliability of the sequencing data. The results showed that the differentially expressed circRNAs potentially regulates the GO-AgNPs induced epigenetic toxicity through a regulatory network consisted of circRNAs, miRNAs and mRNAs. Therefore, the inclusion of epigenetics approaches is essential to assess the biosafety level of GO-AgNPs nanomaterials.

2022-03-31 | GSE199594 | GEO

biosensor-series

Project description:Early life stages are generally most sensitive to toxic effects. Our knowledge on the action of man-made chemicals on the developing vertebrate embryo is, however, rather limited. We exposed zebrafish embryos to 11 of environmental toxicants and measured the changes in gene expression profiles by microarray. Our results demonstrate that the genome of the zebrafish embryo responds to toxicant exposure in a highly sensitive and specific manner. Keywords: toxicants response genes expression profiles

2008-01-03 | GSE9357 | GEO

Testing biological actions of medicinal plants from Northern Vietnam on zebrafish embryos and larvae: developmental, behavioral, and putative therapeutical effects.

Project description:Evaluating the risks and benefits of using traditional medicinal plants is of utmost importance for a huge fraction of the human population, in particular in Northern Vietnam. Zebrafish are increasingly used as a simple vertebrate model for testing toxic and physiological effects of compounds, especially on development. Here, we tested 12 ethanolic extracts from popular medicinal plants collected in Northern Vietnam for their effects on zebrafish survival and development during the first 4 days after fertilization. We characterized more in detail their effects on epiboly, hatching, growth, necrosis, body curvature, angiogenesis, skeletal development and mostly increased movement behavior. Finally, we confirm the effect on epiboly caused by the Mahonia bealei extract by staining the actin filaments and show that this extract also inhibits cell migration of mouse embryo fibroblasts. In conclusion, we show that zebrafish early life stages reveal that traditional medicinal plant extracts are able to affect embryo development to various degrees, prompting caution to apply these medications to pregnant women. In addition, we show that an extract causing delay in epiboly also inhibits mammalian cell migration, suggesting that this effect may serve as a preliminary test for identifying extracts that inhibit cancer metastasis.

2023-03-31 | GSE207770 | GEO

Linkage of genomic biomarkers to whole organism endpoints in a Toxicity Identification Evaluation (TIE)

Project description:Aquatic organisms are exposed to many toxic chemicals and interpreting the cause and effect relationships between occurrence and impairment is difficult. Toxicity Identification Evaluation (TIE) provides a systematic approach for identifying responsible toxicants. TIE relies on relatively uninformative and potentially insensitive toxicological endpoints. Gene expression analysis may provide needed sensitivity and specificity aiding in the identification of primary toxicants. The current work aims to determine the added benefit of integrating gene expression endpoints into the TIE process. A cDNA library and a custom microarray were constructed for the marine amphipod Ampelisca abdita. Phase 1 TIEs were conducted using 10% and 40% dilutions of acutely toxic sediment. Gene expression was monitored in survivors and controls. An expression-based classifier was developed and evaluated against control organisms, organisms exposed to low or medium toxicity diluted sediment, and chemically selective manipulations of highly toxic sediment. The expression-based classifier correctly identified organisms exposed to toxic sediment even when little mortality was observed, suggesting enhanced sensitivity of the TIE process. The ability of the expression-based endpoint to correctly identify toxic sediment was lost concomitantly with acute toxicity when organic contaminants were removed. Taken together, this suggests that gene expression enhances the performance of the TIE process. Wild-collected Ampelisca abdita were exposed to either control (from sites in Long Island Sound, labeled LIS) sediment, toxic (from site on Elizabeth River, labeled ER) sediment, a series of mixtures of LIS and ER sediment, sediments manipulated to alter toxin bioavailability, or toxicant amended sediments. Lethality was scored, and survivors were subjected to mRNA expression analysis via oligo microarray.

2012-12-21 | E-GEOD-41463 | biostudies-arrayexpress

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