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ToxSci Advance Access published online on March 18, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp058
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Rapid sublethal toxicity assessment using bioluminescent Caenorhabditis elegans, a novel whole-animal metabolic biosensor

C. Lagido*, D. McLaggan, A. Flett, J. Pettitt and L.A. Glover

Institute of Medical Sciences, School of Medical sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK

* To whom correspondence should be addressed at the Institute of Medical Sciences, Ashgrove Rd West, Foresterhill, Aberdeen AB25 2 ZD, Scotland, UK. Email: c.lagido{at}abdn.ac.uk; TEL: ++ 44 (0) 1224 555800; FAX: ++ 44 (0) 555844.

Received January 16, 2009; revision received March 2, 2009; accepted March 3, 2009


  Abstract

Sublethal metabolic effects are informative toxicological endpoints. We used a rapid quantitative metabolic endpoint, bioluminescence of firefly luciferase expressing Caenorhabditis elegans, to assess effects of sublethal chronic exposure (19 h) to the oxidative stress agent and environmental pollutant cadmium (provided as chloride salt). Bioluminescence declined in a concentration-dependent manner in the concentration range tested (0- 30 µM Cd), with comparable sensitivity to reproduction and developmental assay endpoints (after 67 and 72 h respectively). Cd concentrations that resulted in 20% reduction in bioluminescence (EC20) were 11.8 -13.0 µM, whereas the reproduction EC20 (67h exposure) was 10.2 µM. At low concentrations of Cd (≤ 15 µM), the decline in bioluminescence reflected a drop in ATP levels. At Cd concentrations of 15 to 30 µM, decreased bioluminescence was attributable both to effects of Cd on ATP levels and decreased production of luciferase proteins, concomitant with a decline in protein levels. We show that whole-animal bioluminescence is a valid toxicological end-point, and a rapid and sensitive predictor of effects of Cd exposure on development and reproduction. This provides a platform for high-throughput sublethal screening and will potentially contribute to reduction of testing in higher animals.

Key Words: Caenorhabditis elegans; sublethal toxicity screening; ATP; firefly luciferase; cadmium.

Email: Cristina Lagido* – c.lagido{at}abdn.ac.uk; Debra McLaggan - d.mclaggan{at}abdn.ac.uk; Aileen Flett – a.w.flett{at}abdn.ac.uk; Jonathan Pettitt – j.pettitt{at}abdn.ac.uk; Anne Glover - l.a.glover{at}abdn.ac.uk


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