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Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene

ABSTRACT: Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to fluoranthene (FA). DEBtox modelling showed an effect of FA on costs for growth and reproduction (i.e. for production of new and differentiated biomass). The microarray analysis supported this effect, showing an effect of FA on protein integrity and turnover that would be expected to have consequences for rates of somatic growth. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE21011 | GEO | 2010/03/23

SECONDARY ACCESSION(S): PRJNA129659

REPOSITORIES: GEO

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Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene

Project description:Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to fluoranthene (FA). DEBtox modelling showed an effect of FA on costs for growth and reproduction (i.e. for production of new and differentiated biomass). The microarray analysis supported this effect, showing an effect of FA on protein integrity and turnover that would be expected to have consequences for rates of somatic growth. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes. Adults of C. elegans strain GE-31 were exposed as biological replicate groups (approx 10,000) to a control and 4 concentrations of fluoranthene from L1 stage. Replicate populations were sampled 12 hours after the on-set of egg laying and hybridised against a common oligonucleotide reference for purposes of normalisation. All experiments were conducted following a reference design with the reference sample compiled from a mixture of RNA extracted from control and cadmium-, fluoranthene-, atrazine- and copper-exposed worms from L1, L4 and adult life-stages. Use of this reference was intended to provide optimal coverage of the spotted genes.

2010-05-05 | E-GEOD-21011 | biostudies-arrayexpress

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium

Project description:Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to cadmium. For Cd, the physiological mode of action as indicated by DEBtox model fitting was an effect on energy assimilation from food, suggesting that the transcriptional response to exposure should be dominated by changes in the expression of transcripts associated with energy metabolism and the mitochondria. While evidence for effect on genes associated with energy production were seen, an ontological analysis also indicated an effect of Cd exposure on DNA integrity and transcriptional activity. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes. Adults of C. elegans strain GE-31 exposed as biological replicate groups (approx 10,000) to a control and 4 concentrations of cadmium from L1 stage. Replicate populations were sampled 12 hours after the on-set of egg laying and hybridised against a common oligonucleotide reference for purposes of normalisation. All experiments were conducted following a reference design with the reference sample compiled from a mixture of RNA extracted from control and cadmium-, fluoranthene-, atrazine- and copper-exposed worms from L1, L4 and adult life-stages. Use of this reference was intended to provide optimal coverage of the spotted genes.

2010-05-05 | E-GEOD-21010 | biostudies-arrayexpress

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine

Project description:Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to atrazine (AZ). For AZ, the physiological mode of action predicted by DEBtox was increased cost for maintenance. The transcriptional analysis demonstrated that this increase resulted from effects on DNA integrity as indicated by changes in the expression of genes chromosomal repair. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes. Adults of C. elegans strain GE-31 exposed as biological replicate groups (approx 10,000) to a control and 4 concentrations of atrazine from L1 stage. Replicate populations were sampled 12 hours after the on-set of egg laying and hybridised against a common reference for purposes of normalisation. All experiments were conducted following a reference design with the reference sample compiled from a mixture of RNA extracted from control and cadmium-, fluoranthene-, atrazine- and copper-exposed worms from L1, L4 and adult life-stages. Use of this reference was intended to provide optimal coverage of the spotted genes.

2010-03-23 | E-GEOD-21008 | biostudies-arrayexpress

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium

2010-03-23 | GSE21010 | GEO

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine

2010-03-23 | GSE21008 | GEO

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans

Project description:This SuperSeries is composed of the following subset Series: GSE21008: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine GSE21010: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium GSE21011: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene Refer to individual Series

2010-03-23 | E-GEOD-21012 | biostudies-arrayexpress

Sub-chronic transcriptional response in adult male MutaTMMouse following oral exposure to benzo(b)fluoranthene in lung, liver, and forestomach tissues [BbF]

Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. Benzo(b)fluoranthene is one such compound. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to benz(a)anthracene in the lung, liver, and forestomach tissues. Adult male MutaTMMouse were exposed to three doses of Benzo(b)fluoranthene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.

2015-10-01 | GSE51315 | GEO

Sub-chronic transcriptional response in adult male MutaTMMouse following oral exposure to benzo(k)fluoranthene in lung, liver, and forestomach tissues [BkF]

Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. Benzo(k)fluoranthen is one such compound. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to benz(a)anthracene in the lung, liver, and forestomach tissues. Adult male MutaTMMouse were exposed to three doses of benzo(k)fluoranthene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.

2015-10-01 | GSE51317 | GEO

Cardiac transcriptome response in developing rainbow trout exposed to retene and fluoranthene

Project description:Newly hatched rainbow trout were exposed to the PAHs retene and fluoranthene semistatically for 1, 3, 7 and 14 days. Fry were exposed to the PAHS alone or as a binary mixture. At sample, hearts were excised, pooled and prepared for microarray analysis. We also investigated body burden of the two PAHs and how the whole organisms respond biometrically following exposure. Transcriptomic responses were confirmed using qPCR.

2021-06-18 | E-MTAB-8980 | biostudies-arrayexpress

D. magna exposed to fluoranthene and pyrene - both as single compounds and binary mixtures

Project description:Daphnia are an important and widely studied model species in ecological and toxicological studies throughout the world and an official (OECD) recommended test organism. Their small size, wide distribution and easy growth conditions make this an organism ideal for functional genomics based studies, including metabolic profiling and transcriptomics. In this study we used an integrated systems approach in which transcriptomic, metabolomic and energetic responses of juvenile (4 days old) daphnids were evaluated in response to exposure to two poly aromatic hydrocarbons (pyrene and fluoranthene) and binary mixtures thereof. In addition, these responses were linked to responses measured during chronic experiments (21 days) assessing survival, growth and reproductive traits. Custom Daphnia magna microarrays were used to assess transcriptomic changes. Hierarchical cluster analysis did not result in a clear distinction between the single compounds suggesting similar molecular modes of action. Cluster analysis with both the single compounds and the binary mixture treatments resulted in a separation of treatments based on differences in toxic ratios rather than component differences. Changes in the metabolic profiles of the organisms were investigated using Nuclear Magnetic Resonance spectroscopy and Gas and Liquid Chromatography Mass Spectrometry. These multivariate metabolomic datasets were analysed with Principal Components Analysis and Partial Least Squares Discriminant Analysis. The major metabolite changes responsible for the differences observed indicated a disturbance in aminosugar metabolism in all cases. The study demonstrates the potential of ’omics’ to provide screening tools for monitoring of the freshwater environment – in invertebrate species - which is reasonably rapid, cost-effective and has the potential to greatly increase the amount of information obtained from aquatic toxicology testing.

2009-12-31 | GSE16869 | GEO

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