Application of physiologically based modelling and transcriptomics to probe the systems toxicology of aldicarb for Caenorhabditis elegans (Maupas 1900).
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.
School of Biosciences, Cardiff University, Park Place, Cardiff, UK.
Jodie F
JF
Wren
Peter
P
Kille
David J
DJ
Spurgeon
Suresh
S
Swain
Stephen R
SR
Sturzenbaum
Tjalling
T
Jager
D000110:Acetylcholinesterase / Q000378:metabolism; D000448:Aldicarb / Q000633:toxicity*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D007306:Insecticides / Q000633:toxicity*; D008018:Life Cycle Stages / Q000187:drug effects; D008954:Models, Biological; D009420:Nervous System / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D000448:Aldicarb; D000110:Acetylcholinesterase
BMC Syst Biol. 2010 Mar 23;4:32
20331876
BMC Genomics. 2006 Jul 07;7:175
16827938
J Nematol. 1991 Jan;23(1):20-7
19283090
Ecotoxicology. 2006 Apr;15(3):305-14
16739032
Environ Sci Technol. 2008 Mar 15;42(6):2181-8
18409656
Mutat Res. 1987 Jun;191(2):99-103
3600695
Nature. 2003 Jan 16;421(6920):231-7
12529635
Dev Biol. 2004 Feb 1;266(1):151-60
14729485
Genetics. 1974 May;77(1):71-94
4366476
Philos Trans R Soc Lond B Biol Sci. 2001 Mar 29;356(1407):331-49
11316483
Aquat Toxicol. 2003 Oct 29;65(2):141-57
12946615
Anal Biochem. 1987 Apr;162(1):156-9
2440339
BMC Biol. 2008 Jun 03;6:25
18522721
Environ Sci Technol. 2004 May 15;38(10):2894-900
15212265
BMC Genomics. 2008 Jun 03;9:266
18522720
Environ Sci Technol. 2008 Jun 1;42(11):4208-14
18589989
J Biol Chem. 2003 Nov 7;278(45):44657-66
12939266
Chemosphere. 2007 Feb;67(1):60-71
17112564
Parasitol Today. 1992 Dec;8(12):406-11
15463554
Environ Toxicol Chem. 2006 Dec;25(12):3230-7
17220093
Genetics. 1993 Apr;133(4):897-917
8462849
Mutat Res. 1984 Nov-Dec;138(2-3):175-9
6513973
BMC Genet. 2005 Feb 07;6:5
15698479
J Cell Biol. 1987 Dec;105(6 Pt 1):2763-70
3320053