Schwab B W, Murphy S D
J Toxicol Environ Health. 1981 Jul-Aug;8(1-2):199-204. doi: 10.1080/15287398109530063.
The induction of anticholinesterase tolerance has, in the past, been achieved by using multiple doses of organophosphorus ester insecticides that initially caused cholinergic signs. The purpose of this study was to ascertain whether anticholinesterase tolerance could be induced with doses of an anticholinesterase that produced no overt cholinergic signs. Rats were fed diets containing 0, 7.5, or 20 ppm disulfoton. Animals fed at the 7.5 ppm level were without cholinergic signs throughout the period of feeding. Rats from this group were significantly more resistant to the lethal effect of carbachol than rats given the control diet after 58 and 62 d on the diet. Animals fed 20 ppm disulfoton in the diet initially showed signs that gradually disappeared with time on the diet. Rats fed at this level were more resistant to the lethal effect of carbachol than controls on all challenge dates (30, 45, 58, and 62 d on the diets) and more resistant than animals fed 7.5 ppm only on d 38 and 45. Thus the organophosphorus ester insecticide disulfoton, fed to rats in a dietary concentration that depressed acetylcholinesterase but was insufficient to cause cholinergic signs, induced tolerance to the lethal effects of carbachol. The length of time on an experimental diet before resistance to carbachol could be demonstrated was greater for the experimental group given 7.5 ppm disulfoton than the group given 20 ppm disulfoton in the diet.
过去，抗胆碱酯酶耐受性的诱导是通过使用多剂量的有机磷酸酯杀虫剂来实现的，这些杀虫剂最初会引起胆碱能症状。本研究的目的是确定是否可以用不会产生明显胆碱能症状的抗胆碱酯酶剂量来诱导抗胆碱酯酶耐受性。给大鼠喂食含有0、7.5或20 ppm乙拌磷的日粮。以7.5 ppm水平喂食的动物在整个喂食期间没有胆碱能症状。在喂食日粮58天和62天后，该组大鼠对卡巴胆碱的致死作用的抵抗力明显高于喂食对照日粮的大鼠。日粮中喂食20 ppm乙拌磷的动物最初表现出一些症状，但随着喂食时间的延长逐渐消失。在所有挑战日期（喂食日粮的第30、45、58和62天），以该水平喂食的大鼠对卡巴胆碱致死作用的抵抗力均高于对照组，并且在第38天和第45天比仅喂食7.5 ppm的动物更具抵抗力。因此，以饮食浓度喂食大鼠的有机磷酸酯杀虫剂乙拌磷，其降低了乙酰胆碱酯酶活性，但不足以引起胆碱能症状，从而诱导了对卡巴胆碱致死作用的耐受性。对于日粮中给予7.5 ppm乙拌磷的实验组，在能够证明对卡巴胆碱具有抗性之前，在实验日粮上的喂食时间比给予20 ppm乙拌磷的组更长。
