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

Swain, Suresh; Wren, Jodie F.; Stürzenbaum, Stephen R.; Kille, Peter; Morgan, A. John; Jager, Tjalling; Jonker, Martijs J.; Hankard, Peter K.; Svendsen, Claus ORCID: https://orcid.org/0000-0001-7281-647X; Chaseley, Jenifer; Hedley, B. Ann; Blaxter, Mark; Spurgeon, David J. ORCID: https://orcid.org/0000-0003-3264-8760. 2010 Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans. BMC Systems Biology, 4 (32). https://doi.org/10.1186/1752-0509-4-32

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Abstract/Summary

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:	Publication - Article
Digital Object Identifier (DOI):	https://doi.org/10.1186/1752-0509-4-32
Programmes:	CEH Topics & Objectives 2009 - 2012 > Biodiversity > BD Topic 1 - Observations, Patterns, and Predictions for Biodiversity CEH Topics & Objectives 2009 - 2012 > Biogeochemistry > BGC Topic 1 - Monitoring and Interpretation of Biogeochemical and Climate Changes CEH Topics & Objectives 2009 - 2012 > Biodiversity > BD Topic 2 - Ecological Processes in the Environment
UKCEH and CEH Sections/Science Areas:	Hails
ISSN:	1752-0509
Additional Information. Not used in RCUK Gateway to Research.:	BMC Systems Biology is an Open Access journal and full text can be accessed via the OFFICIAL URL link
NORA Subject Terms:	Biology and Microbiology
Date made live:	07 Sep 2010 08:53 +0 (UTC)
URI:	https://nora.nerc.ac.uk/id/eprint/10902

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