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有机磷杀虫剂敌百虫、乐果、亚胺硫磷和溴硫磷对小鼠体内鸟嘌呤N7-烷基化作用的比较研究

A comparative study of guanine N7-alkylation in mice in vivo by the organophosphorus insecticides trichlorphon, dimethoate, phosmet and bromophos.

作者信息

Dedek W, Grahl R, Schmidt R

出版信息

Acta Pharmacol Toxicol (Copenh). 1984 Aug;55(2):104-9. doi: 10.1111/j.1600-0773.1984.tb01970.x.

Abstract

Following intraperitoneal administration to male mice (strain AB Jena/Halle) of 14C-methyl-labelled trichlorphon, dimethoate, phosmet and bromophos, 10-20 Ci/mol, in dosages of 0.06-0.55 mmol/kg, DNA from liver and kidneys was analyzed for 14C in N-7 methylguanine (7-MeG). The extents of methylation were in the range of 5-10 mumol 7-MeG/mol guanine for trichlorphon and dimethoate and of 0.2-0.4 for phosmet and bromophos, for high doses, respectively Excretion half-lives of 7-MeG were differing between trichlorphon (5 hrs, high dose, and 15-17 hrs, low dose) and dimethoate (23-160 hrs, high dose). The extents of methylation at 0-6 of guanine were estimated to be around 0.01 mumol 0-6 MeG/mol guanine for high doses of organophosphates of sufficient water solubility. Factors associated with the partition of organophosphates in mammalian systems are useful for estimating DNA attack by organophosphates in mammals in vivo.

摘要

将10 - 20居里/摩尔、剂量为0.06 - 0.55毫摩尔/千克的14C - 甲基标记的敌百虫、乐果、亚胺硫磷和溴硫磷经腹腔注射给雄性小鼠(AB耶拿/哈雷品系)后,分析肝脏和肾脏DNA中的N - 7甲基鸟嘌呤(7 - MeG)中的14C。高剂量时,敌百虫和乐果的甲基化程度在5 - 10微摩尔7 - MeG/摩尔鸟嘌呤范围内,亚胺硫磷和溴硫磷的甲基化程度分别为0.2 - 0.4。7 - MeG的排泄半衰期在敌百虫(高剂量时为5小时,低剂量时为15 - 17小时)和乐果(高剂量时为23 - 160小时)之间有所不同。对于高剂量的具有足够水溶性的有机磷酸酯,鸟嘌呤0 - 6位的甲基化程度估计约为0.01微摩尔0 - 6 MeG/摩尔鸟嘌呤。与有机磷酸酯在哺乳动物系统中的分配相关的因素有助于估计有机磷酸酯在哺乳动物体内对DNA的攻击。

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