Reversible AChE inhibitors in C. elegans vs. rats, mice.
We are investigating whether Caenorhabditis elegans could be used as a screen for vertebrates by comparing the responses of components of its cholinergic system to well-characterized toxicants. We assessed whether C. elegans displays similar toxicity as rats and mice to reversible acetylcholinesterase (AChE) inhibitors, and sought to corroborate that the toxicity mechanism is the same. To determine relative potencies, movement-concentration curves were generated, 50th percentiles for movement were located, ranked and compared statistically to rat and mouse oral acute LD50s. The ranking was significantly correlated to rat and mouse rankings (alpha=0.05). We measured a concentration-dependent decrease in AChE activity correlating to a decrease in movement for each carbamate, suggesting that the mechanism of toxicity is the same. Finally, as seen in mammals, inhibition of AChE activity occurred before a movement decrease. The response of C. elegans to carbamate exposure shows significant correlation to rat and mouse data.
Melstrom
Paul C
PC
Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA.
Williams
Phillip L
PL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D017173:Caenorhabditis elegans / Q000187:drug effects*; D002219:Carbamates / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007928:Lethal Dose 50; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D013045:Species Specificity
D002219:Carbamates; D002800:Cholinesterase Inhibitors