In vivo and in vitro resistance to multiple anticholinesterases in Xenopus laevis tadpoles.

Natural and man-made anticholinesterases comprise a significant share of the Xenobiotic poisons to which many living organisms are exposed. To evaluate the potential correlation between the resistance of acetylcholinesterase (AChE) to such toxic agents and the systemic toxicity they confer, we characterized the sensitivity of AChE from Xenopus laevis tadpoles to inhibitors, examined the susceptibility of such tadpoles to poisoning by various anticholinesterases and tested the inhibitor sensitivities of recombinant human AChE produced in these amphibian embryos from microinjected DNA. Our findings reveal exceptionally high resistance of Xenopus AChE to carbamate, organophosphate and quaternary anticholinesterases. In spite of the effective in vivo penetrance to Xenopus tadpole tissues of paraoxon, the poisonous metabolite of the pro-insecticide parathion, the amphibian embryos displayed impressive resistance to this organophosphorous agent. The species specificity of this phenomenon was clearly displayed in Xenopus tadpoles expressing recombinant human AChE, which was far more sensitive than the frog enzyme to in vivo paraoxon inhibition. Our findings demonstrate a clear correlation between AChE susceptibility to enzymatic inhibition and the systemic toxicity of anticholinesterases and raise a serious concern regarding the use of Xenopus tadpoles for developmental toxicology tests of anticholinesterases.