Dataset Information

How nanomolar doses of combined metal salts (Cd, Cu, Hg) induce DNA damage and transcriptional changes in the gills of Mytilus galloprovincialis.

ABSTRACT: We used a cDNA microarray previously defined for the marine sentinel organism Mytilus galloprovincialis (MytArray1.0) to evaluate the effects of nanomolar doses of combined metal salts (50, 100 and 200 nM mixtures of Cd, Cu and Hg) after 48 hours of mussel exposure. Pointing to the mussel gills, first target of toxic water contaminants and actively proliferating tissue, we found significant dose-related increases of cells with micronuclei and other nuclear abnormalities in the treated mussels, with differences in the bioconcentration of the three metals determined in the mussel pulp by atomic absorption spectrometry. Following gill RNA purification and DNA microarray analysis, individual gene expression profiles revealed some transcriptional changes at the 50 nM dose, and substantial increases of differentially expressed genes at the 100 and 200 nM doses with roughly similar amounts of up- and down-regulated signals. The functional annotation of transcripts with consistent expression trends and significantly altered at least in one dose point disclosed the complexity of the induced cell response.

ORGANISM(S): Mytilus galloprovincialis

PROVIDER: GSE41218 | GEO | 2013/06/30

SECONDARY ACCESSION(S): PRJNA176220

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Development of radiation medical countermeasures under the U.S. Food and Drug Administration Animal Rule requires the capability to translate an effective animal to human drug dose. One method of human dose translation is using a biomarker and determining drug doses that modulate the biomarker to the desired level. BIO 300 Oral Powder (BIO 300) is a prophylactic radiation medical countermeasure that is currently being developed following the Animal Rule. The present study aimed to identify biomarkers that can be used for human dose conversion by conducting transcriptomics of whole blood collected from BIO 300-treated CD2F1 mice in the presence and absence of total-body irradiation (TBI). Mice were treated with vehicle or 50, 100 or 200 mg/kg BIO 300, twice daily, for 6 days. Whole blood samples were collected 24 and 48 h after the last dose of the drug. Animals were also treated with vehicle or 200 mg/kg BIO 300 for 6 days prior to 9.2 Gy TBI 24 h after the last dose, with blood collection 24 h after irradiation. RNA sequencing demonstrated 100 – 200 mg/kg doses caused significantly more differential gene expression at 48 h post-drug dose compared to 50 mg/kg. Pathway analysis of the transcriptome profile from vehicle-treated/radiation-exposed mice revealed that many inflammatory signaling pathways were activated in these animals. Signaling pathways enriched in BIO 300-treated/TBI mice were involved in cellular stress and immune response and were predicted to be inhibited. We also identified pathways that were in inverse states (activation/inhibition) in vehicle and BIO 300-treated mice with TBI. There were two pathways specifically activated in vehicle-treated animals with TBI and inhibited in BIO 300-treated animals (with or without TBI), pathogen-induced cytokine storm signaling and S100 family signaling. In comparison to previously published human data, pulmonary fibrosis idiopathic signaling and wound healing signaling were enriched in healthy volunteers treated with BIO 300 and BIO 300-treated mice with TBI. In all, four signaling pathways were identified that were activated in vehicle-treated animals exposed to total body radiation but inhibited in irradiated animals or healthy humans treated with BIO 300. These pathways should be explored to identify potential biomarkers of BIO 300 that can be used for human dose translation.

Dataset Information

How nanomolar doses of combined metal salts (Cd, Cu, Hg) induce DNA damage and transcriptional changes in the gills of Mytilus galloprovincialis.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets