In vivo and in vitro resistance to multiple anticholinesterases in Xenopuslaevis tadpoles

Natural and man-made anticholinesterases comprise a significant share of th e Xenobiotic poisons to which many living organisms are exposed. To evaluat e the potential correlation between the resistance of acetylcholinesterase (AChE) to such toxic agents and the systemic toxicity they confer, we chara cterized the sensitivity of AChE from Xenopus laevis tadpoles to inhibitors , examined the susceptibility of such tadpoles to poisoning by various anti cholinesterases and tested the inhibitor sensitivities of recombinant human AChE produced in these amphibian embryos from microinjected DNA. Our findi ngs reveal exceptionally high resistance of Xenopus AChE to carbamate, orga nophosphate and quaternary anticholinesterases. In spite of the effective i n vivo penetrance to Xenopus tadpole tissues of paraoxon, the poisonous met abolite of the pro-insecticide parathion, the amphibian embryos displayed i mpressive resistance to this organophosphorous agent. The species specifici ty of this phenomenon was clearly displayed in Xenopus tadpoles expressing recombinant human AChE, which was far more sensitive than the frog enzyme t o in vivo paraoxon inhibition. Our findings demonstrate a clear correlation between AChE susceptibility to enzymatic inhibition and the systemic toxic ity of anticholinesterases and raise a serious concern regarding the use of Xenopus tadpoles for developmental toxicology tests of anticholinesterases . (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.