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Application of physiologically based modelling and transcriptomics to probe the systems toxicology of aldicarb for Caenorhabditis elegans (Maupas 1900).

Wren JF, Kille P, Spurgeon DJ, Swain S, Sturzenbaum SR, Jager T - Ecotoxicology (2011)

Bottom Line: A clear effect of aldicarb on nematode movement was found suggesting that this pesticide acts as a neurotoxicant.Aldicarb also had an effect on life cycle traits including low concentration life-span extension; high concentration brood size reduction and a high concentration extension of time to first egg.These effects, coupled to the effect on biotransformation enzymes also seen, represent the materialisation of the maintenance costs indicated by DEBtox modelling.

View Article: PubMed Central - PubMed

Affiliation: School of Biosciences, Cardiff University, Park Place, Cardiff, UK.

ABSTRACT
The toxicity of aldicarb on movement, life cycle, population growth rate and resource allocation, and the gene expression changes underpinning these effects, were investigated for Caenorhabditis elegans. A clear effect of aldicarb on nematode movement was found suggesting that this pesticide acts as a neurotoxicant. Aldicarb also had an effect on life cycle traits including low concentration life-span extension; high concentration brood size reduction and a high concentration extension of time to first egg. All life-cycle and growth data were integrated into a biology-based model (DEBtox) to characterise aldicarb effects on life-history traits, resource allocation and population growth rate within a single modelling framework. The DEBtox fits described concentration dependent effects on individual traits and population growth rate and indicated that the most probable mechanism of action of the pesticide was an increase in energy demands for somatic and reproductive tissue maintenance. Transcriptomic profiling indicated that aldicarb was associated with changes in amino acid metabolism, DNA structure, fatty acid metabolism and cytochrome P450 mediated xenobiotic metabolism. The changes in the amino acid and fatty acid pathways suggest an effect of aldicarb on protein integrity; while effects on DNA suggests that aldicarb influence DNA morphology or replication. Both these effects have the potential to incur increased costs for structural maintenance of macromolecules. These effects, coupled to the effect on biotransformation enzymes also seen, represent the materialisation of the maintenance costs indicated by DEBtox modelling.

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Related in: MedlinePlus

Intensity levels of genes involved with chromatin assembly and DNA packaging which were upregulated in response to aldicarb, means are semilog plotted, error bars represent standard error of the mean, control showing as unshaded bars, aldicarb exposed nematode (16 mg/l) as shaded bars; dashed line of two-fold induction
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Fig4: Intensity levels of genes involved with chromatin assembly and DNA packaging which were upregulated in response to aldicarb, means are semilog plotted, error bars represent standard error of the mean, control showing as unshaded bars, aldicarb exposed nematode (16 mg/l) as shaded bars; dashed line of two-fold induction

Mentions: Gene Ontology (GO) annotation analysis in GeneSpring GX was used to identify biochemical pathways affected by aldicarb. Only 40% of the gene list was annotated (167 out of the 380 up-regulated genes, and 95 of the 282 down-regulated genes), thus the pathways highlighted can only claim to represent a snap-shot of all potential responses of C. elegans to aldicarb. Nevertheless, biological processes were identified that were statistically over-represented in the up-regulated gene list. These related to chromosome organization and biogenesis (GO:7001), protein metabolism (GO:19538), macromolecule catabolism (GO:9057), protein ubiquitination (GO:16567), ubiquitin cycle (GO:6512), osmoregulation (GO:18987), and ageing/determination of adult lifespan (GO:7568, GO:8340) (Table 2). The effects on DNA and chromosome structures were notable (p < 0.001), with a number of genes including multiple histones and genes involved in heterochromatin assembly being upregulated up to four fold in response to aldicarb exposure (Fig. 4). No GO terms represented by more than ten genes were over-represented in the significantly down-regulated gene list.Table 2


Application of physiologically based modelling and transcriptomics to probe the systems toxicology of aldicarb for Caenorhabditis elegans (Maupas 1900).

Wren JF, Kille P, Spurgeon DJ, Swain S, Sturzenbaum SR, Jager T - Ecotoxicology (2011)

Intensity levels of genes involved with chromatin assembly and DNA packaging which were upregulated in response to aldicarb, means are semilog plotted, error bars represent standard error of the mean, control showing as unshaded bars, aldicarb exposed nematode (16 mg/l) as shaded bars; dashed line of two-fold induction
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037492&req=5

Fig4: Intensity levels of genes involved with chromatin assembly and DNA packaging which were upregulated in response to aldicarb, means are semilog plotted, error bars represent standard error of the mean, control showing as unshaded bars, aldicarb exposed nematode (16 mg/l) as shaded bars; dashed line of two-fold induction
Mentions: Gene Ontology (GO) annotation analysis in GeneSpring GX was used to identify biochemical pathways affected by aldicarb. Only 40% of the gene list was annotated (167 out of the 380 up-regulated genes, and 95 of the 282 down-regulated genes), thus the pathways highlighted can only claim to represent a snap-shot of all potential responses of C. elegans to aldicarb. Nevertheless, biological processes were identified that were statistically over-represented in the up-regulated gene list. These related to chromosome organization and biogenesis (GO:7001), protein metabolism (GO:19538), macromolecule catabolism (GO:9057), protein ubiquitination (GO:16567), ubiquitin cycle (GO:6512), osmoregulation (GO:18987), and ageing/determination of adult lifespan (GO:7568, GO:8340) (Table 2). The effects on DNA and chromosome structures were notable (p < 0.001), with a number of genes including multiple histones and genes involved in heterochromatin assembly being upregulated up to four fold in response to aldicarb exposure (Fig. 4). No GO terms represented by more than ten genes were over-represented in the significantly down-regulated gene list.Table 2

Bottom Line: A clear effect of aldicarb on nematode movement was found suggesting that this pesticide acts as a neurotoxicant.Aldicarb also had an effect on life cycle traits including low concentration life-span extension; high concentration brood size reduction and a high concentration extension of time to first egg.These effects, coupled to the effect on biotransformation enzymes also seen, represent the materialisation of the maintenance costs indicated by DEBtox modelling.

View Article: PubMed Central - PubMed

Affiliation: School of Biosciences, Cardiff University, Park Place, Cardiff, UK.

ABSTRACT
The toxicity of aldicarb on movement, life cycle, population growth rate and resource allocation, and the gene expression changes underpinning these effects, were investigated for Caenorhabditis elegans. A clear effect of aldicarb on nematode movement was found suggesting that this pesticide acts as a neurotoxicant. Aldicarb also had an effect on life cycle traits including low concentration life-span extension; high concentration brood size reduction and a high concentration extension of time to first egg. All life-cycle and growth data were integrated into a biology-based model (DEBtox) to characterise aldicarb effects on life-history traits, resource allocation and population growth rate within a single modelling framework. The DEBtox fits described concentration dependent effects on individual traits and population growth rate and indicated that the most probable mechanism of action of the pesticide was an increase in energy demands for somatic and reproductive tissue maintenance. Transcriptomic profiling indicated that aldicarb was associated with changes in amino acid metabolism, DNA structure, fatty acid metabolism and cytochrome P450 mediated xenobiotic metabolism. The changes in the amino acid and fatty acid pathways suggest an effect of aldicarb on protein integrity; while effects on DNA suggests that aldicarb influence DNA morphology or replication. Both these effects have the potential to incur increased costs for structural maintenance of macromolecules. These effects, coupled to the effect on biotransformation enzymes also seen, represent the materialisation of the maintenance costs indicated by DEBtox modelling.

Show MeSH
Related in: MedlinePlus