Toxicology studies in Caenorhabditis elegans

Budd, Chloe Denisha (2008) Toxicology studies in Caenorhabditis elegans. MRes thesis, University of Nottingham.

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The nematode Caenorhabditis elegans was established as a model organism to study in 1965. In this study, C.elegans are used as a model system in which to examine the possible mechanisms of toxicity caused in humans by the anti-malarial drugs quinine and chloroquine, as well as toxicity caused in rodents by furan and investigating the pharmacology of the insecticides DDT and deltamethrin and how they affect invertebrates.

Toxicity assays were used to determine what effects these 5 toxins have on C.elegans at different stages of its life cycle. The effects on growth, brood size and lethality were determined using three types of assays. These assays were robust, producing reproducible results and identifying specific toxicity.

The results of these assays enabled the identification of a phenotype for each type of assay, and the inhibiting concentration (if any), for all the toxins tested.

Quinine had a dose-dependent inhibitory effect on larval growth and brood size.

Chloroquine, furan and DDT all had an inhibitory effect on growth, brood size and lethality of C.elegans. Chloroquine and DDT showed a greater potency on larval growth while furan showed a higher potency on brood size. Deltamethrin showed inhibitory effects on larval growth but showed no significant effect to the brood size and lethality of C.elegans. Deltamethrin shows stage-specific toxicity, as larval growth is significantly inhibited and effects on brood size and lethality are insignificant.

The lat-1 (ok1465) C.elegans strain has a 2209bp deletion of the lat-1 gene, and approximately 97% of these worms die before adulthood, with only 2-3 adult offspring per animal. The lat-1 (ok1465) C.elegans was crossed with the CB4856 (Hawaiian) wild-type C.elegans strain for 6 generations to produce a strain with the ok1465 allele in a Hawaiian C.elegans background.

A mutagenesis could then be performed to screen and select for mutants that were resistant to the effects of the drug tested at concentrations that are toxic to wild-type animals. In the case of lat-1 (ok1465) C.elegans, screening would be to identify mutant individuals that no longer showed lethality; a resistant mutant would produce 300+ viable offspring. Gene mapping would then be used to identify these mutations.

The hypothesis is that for the toxins tested, the mechanism by which they exert their toxic effects in C.elegans would be the same as for mammals and invertebrates.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Bell, D.R.
Keywords: C.elegans
Subjects: Q Science > QL Zoology > QL360 Invertebrates
Faculties/Schools: UK Campuses > Faculty of Science > School of Biosciences
Item ID: 10613
Depositing User: EP, Services
Date Deposited: 12 Jan 2009
Last Modified: 16 Dec 2017 06:31

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