Transcriptomics

Dataset Information

3

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


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 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.

ORGANISM(S): Caenorhabditis elegans  

SUBMITTER: Jodie F Wren   Claus Svendsen  Jenifer Owen  Suresh Swain  Tjalling Jager  Peter Kille  David J Spurgeon  Stephen R Sturzenbaum  A J Morgan  Mark L Blaxter  Peter K Hankard  B A Hedley  Martijs J Jonker 

PROVIDER: E-GEOD-21010 | ArrayExpress | 2010-05-05

SECONDARY ACCESSION(S): GSE21010PRJNA129657

REPOSITORIES: GEO, ArrayExpress

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

Swain Suresh S   Wren Jodie F JF   Stürzenbaum Stephen R SR   Kille Peter P   Morgan A John AJ   Jager Tjalling T   Jonker Martijs J MJ   Hankard Peter K PK   Svendsen Claus C   Owen Jenifer J   Hedley B Ann BA   Blaxter Mark M   Spurgeon David J DJ  

BMC systems biology 20100323


BACKGROUND: 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 three toxic chemicals: cadmium, fluoranthene (FA) and atrazine (AZ). RESULTS: For Cd, the physiological mode of action as indicated by DEBtox model fitting was an  ...[more]

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