title: Rapid sublethal toxicity assessment using bioluminescent Caenorhabditis elegans, a novel whole-animal metabolic biosensor.
abstract: Sublethal metabolic effects are informative toxicological end points. We used a rapid quantitative metabolic end point, 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 microM Cd), with comparable sensitivity to reproduction and developmental assay end points (after 67 and 72 h, respectively). Cd concentrations that resulted in 20% reduction in bioluminescence (EC(20)) were 11.8-13.0 microM, whereas the reproduction EC(20) (67 h exposure) was 10.2 microM. At low concentrations of Cd (< or = 15 microM), the decline in bioluminescence reflected a drop in ATP levels. At Cd concentrations of 15-30 microM, 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.
authors.affiliation: Institute of Medical Sciences, School of Medical sciences, University of Aberdeen, Foresterhill, Aberdeen AB252ZD, Scotland, UK. c.lagido@abdn.ac.uk
authors.forename: Cristina
authors.initials: C
authors.lastname: Lagido
authors.forename: Debbie
authors.initials: D
authors.lastname: McLaggan
authors.forename: Aileen
authors.initials: A
authors.lastname: Flett
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pettitt
authors.forename: L Anne
authors.initials: LA
authors.lastname: Glover
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques; D019256:Cadmium Chloride / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D049409:Luciferases, Firefly / Q000378:metabolism*; D008163:Luminescent Measurements; D012098:Reproduction / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D029742:Caenorhabditis elegans Proteins; D000255:Adenosine Triphosphate; D049409:Luciferases, Firefly; D019256:Cadmium Chloride