Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, S-752 36 Uppsala, Sweden.
Environ Toxicol Pharmacol. 1996 Dec 20;2(4):307-14. doi: 10.1016/s1382-6689(96)00062-2.
This study revealed increased susceptibility in adult mice, exposed neonatally to a low dose of DDT (1,1,1-trichloro-2,2-bis( p-chlorofenyl)ethane), to develop changes in behaviour and cholinergic muscarinic receptors when exposed as adults to the organophosphorus insecticide paraoxon. 10-day-old NMRI male mice were given a single oral dose of DDT (0.5 mg/kg body weight). At the age of 5 months, paraoxon was administered by gavage as a single dose (0.7 or 1.4 mg/kg body weight) every 2nd day for 1 week. These doses caused approximately 15% and 45% inhibition of acetylcholinesterase respectively, 48 h after the last exposure. 24 h after the last paraoxon administration, a spontaneous motor activity test revealed no differences between any of the adult paraoxon-treated mice and their corresponding controls, though when the test was performed again 2 months later, mice exposed neonatally to DDT and given paraoxon as adults had developed changes in spontaneous behaviour. The density of muscarinic cholinergic receptors was significantly increased in this group. No significant changes were seen in either behaviour or muscarinic receptors in mice exposed neonatally to the vehicle and receiving paraoxon as adults and there were no significant differences in the muscarinic or nicotinic subpopulations investigated, between any of the treatment groups. These results show that a dose of paraoxon not having any effect in vehicle-treated animals can cause effects in animals neonatally exposed to DDT.
本研究揭示，新生期接触低剂量滴滴涕（1,1,1-三氯-2,2-双（对氯苯基）乙烷）的成年小鼠在成年期接触有机磷杀虫剂对氧磷时，行为和毒蕈碱型乙酰胆碱能受体发生变化的易感性增加。10 日龄 NMRI 雄性小鼠给予滴滴涕（0.5mg/kg 体重）单次口服剂量。在 5 月龄时，通过灌胃给予对氧磷，作为单次剂量（0.7 或 1.4mg/kg 体重），每 2 天给予 1 次，共 1 周。最后一次接触后 48 小时，这些剂量分别导致乙酰胆碱酯酶抑制约 15%和 45%，最后一次给予对氧磷 24 小时后，自发运动活性测试显示，任何成年对氧磷处理组的小鼠与其相应的对照组之间均无差异，尽管在 2 个月后再次进行测试时，新生期接触滴滴涕并成年期给予对氧磷的小鼠的自发行为发生了变化。在该组中，毒蕈碱型乙酰胆碱能受体的密度显著增加。在新生期接触载体并成年期接受对氧磷的小鼠中，行为或毒蕈碱受体均未发生显著变化，在所研究的毒蕈碱或烟碱亚群中，任何处理组之间均无显著差异。这些结果表明，在载体处理的动物中没有任何作用的对氧磷剂量可以在新生期接触滴滴涕的动物中引起作用。
