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

Swain, Suresh, Wren, Jodie, Sturzenbaum, Stephen, Kille, Peter, Morgan, A. John, Jager, Tjalling, Jonker, Martijs, Hankard, Peter, Svendsen, Claus, Owen, Jennifer Ruth, Hedley, B. Ann, Blaxter, Mark and Spurgeon, David J. 2010. Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans. BMC Systems Biology 4 (1) , 32. 10.1186/1752-0509-4-32

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Abstract

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 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. 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. 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. Conclusions: 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Publisher: Biomed Central
ISSN: 1752-0509
Date of First Compliant Deposit: 30 March 2016
Last Modified: 10 Oct 2017 14:10
URI: http://orca-mwe.cf.ac.uk/id/eprint/25742

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