Johansson U, Fredriksson A, Eriksson P
Department of Environmental Toxicology, Uppsala University, Sweden.
Eur J Pharmacol. 1995 Jul 1;293(2):159-66. doi: 10.1016/0926-6917(95)00012-7.
We recently reported changes in the density of muscarinic acetylcholine receptors in cerebral cortex of mice treated neonatally with DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane) and receiving bioallethrin as adults. We also found behavioural aberrations in adult mice treated with bioallethrin, whether neonatally treated with DDT or the vehicle. To ascertain whether these changes were permanent, 10-day-old mice received an oral dose of DDT (0.5 mg/kg body weight) and at the age of 5 months they received bioallethrin orally (0.7 mg/kg body weight/day; 7 days). The animals were investigated at the age of 7 months. Here we report muscarinic acetylcholine receptor changes, additional behavioural disturbances and learning disabilities in mice receiving DDT as neonates and bioallethrin as adults, whereas the behavioural disturbances in mice receiving vehicle as neonates and bioallethrin as adults had diminished and changes in proportions of high- and low-affinity binding sites had developed. No changes in the density of nicotinic acetylcholine receptors were noted for any of the treated groups. In conclusion, exposure of neonates to DDT leads to increased susceptibility in adults to a short-acting pesticide with similar neurotoxic action. An adult exposure to this short-acting pesticide to mice neonatally exposed to DDT leads to irreversible muscarinic acetylcholine receptor changes and behavioural disturbances with additional changes 2 months after the exposure.
我们最近报告了新生期用滴滴涕（1,1,1-三氯-2,2-双（对氯苯基）乙烷）处理且成年后接触生物菊酯的小鼠大脑皮质中毒蕈碱型乙酰胆碱受体密度的变化。我们还发现，无论新生期是用滴滴涕还是赋形剂处理，成年后用生物菊酯处理的小鼠都存在行为异常。为确定这些变化是否是永久性的，10日龄小鼠口服一剂滴滴涕（0.5毫克/千克体重），5月龄时口服生物菊酯（0.7毫克/千克体重/天；共7天）。在7月龄时对这些动物进行研究。在此我们报告，新生期接受滴滴涕处理且成年后接受生物菊酯处理的小鼠存在毒蕈碱型乙酰胆碱受体变化、额外的行为障碍和学习障碍，而新生期接受赋形剂处理且成年后接受生物菊酯处理的小鼠行为障碍有所减轻，且高亲和力和低亲和力结合位点的比例发生了变化。任何处理组的烟碱型乙酰胆碱受体密度均未观察到变化。总之，新生期接触滴滴涕会导致成年后对具有类似神经毒性作用的短效杀虫剂的易感性增加。成年后对新生期接触过滴滴涕的小鼠施用这种短效杀虫剂会导致毒蕈碱型乙酰胆碱受体发生不可逆变化以及行为障碍，且在接触后2个月会出现额外变化。
