As a widely studied and convenient model organism, C. elegans could be a useful tool in the investigation of in vivo metabolism.' A clear understanding ·of the molecular response to chemical exposure is required across a broad range of disciplines, from pharmacology to pesticide development. B-naphthoflavone, chloroquine, dazomet, imidacloprid, juglone and thiabendazole were selected for study. Touch respons~ assays were employed to monitor the responses of wild-type C. elegans to. different concentrations of chemical over 72 hours and the associated transcriptional response was analysed by whole genome microarray. Populations exposed to the six chemicals over 1 hour and 48 hours were compared to those subjected to osmotic and thermal stress, as well as to unstressed controls. Concerted changes' in the C. elegans transcriptome occur in response to exposure to specific chemicals. A large proportion of responsive genes encode enzymes with a known metabolic role, some with human homologues, predominantly cytochrome P450s, glutathione S-tranferases and UDPglucuronosyltransferases. Genes that encode nuclear hormone receptors and signalling molecules were also up-regulated, and future research will reveal whether they have a role in mediating the response to xenobiotic exposure. Other genes identified included nematode-specific genes, and genes of unknown function with mammal{an homologues. Genes ,encoding the antimicrobial thaumatins and caenacins were up-regulated in response to xenobiotic exposure. Others of the up-regulated genes encode signalling molecules that have been shown to coordinate responses to biotic stress. Taken together these results suggest that there is overlap between the responses to biotic and xenobiotic challenge. A green fluorescent C. elegans reporter strain was produced that describes . the cellular location of the up-regulation of cyp-35A5 by p- naphthoflavone and thiabendazole. This proof of principle provides the potential for panels of such reporters to be used in further investigations of meta,bolism of xenobiotic compounds in C. elegans.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:485202 |
| Date | January 2007 |
| Creators | Broad, Samantha Jayne |
| Publisher | University of Leeds |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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