Metabolism of [14C]trichloroethylene to 14CO2 and interaction of a metabolite with liver DNA in rats and mice.
Metabolism of [14C]trichloroethylene to 14CO2 and interaction of a metabolite with liver DNA in rats and mice.
复制标题
[14C]三氯乙烯在大鼠和小鼠中代谢为 14CO2 以及代谢物与肝脏 DNA 的相互作用。
DOI：
10.1080/15287398209530204
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Magee,PN
中科院分区：
文献类型：
--
作者：
Parchman,LG;Magee,PN
雄性 Sprague-Dawley 大鼠和雄性 B6C3F1 小鼠在腹腔注射单剂量玉米油载体后 24 小时内，以 14CO2 形式排泄 5-15% 示踪剂剂量的 [14C]三氯乙烯。小鼠中以CO2形式排出的剂量比例高于大鼠，但饥饿或苯巴比妥预处理后大鼠中以CO2形式排出的剂量比例增加。随着剂量增加至LD50水平，以14CO2形式排泄的比例略有下降，但这主要是由于未变化的三氯乙烯的损失增加。因此， 14 CO 2 的排泄与三氯乙烯微粒体代谢为能够结合谷胱甘肽或大分子的亲电中间体的预期水平相关。观察到肝脏蛋白标记相对较高（小鼠中为 10,000–23,000 cpm/mg），而 DNA 标记始终观察到非常低，无法通过高效液相色谱 (HPLC) 鉴定任何加合物。此外，注射 LD50 剂量的三氯乙烯后，碱性蔗糖梯度离心对 DNA 片段化没有影响。因此观察到三氯乙烯在体内与DNA相互作用的能力非常弱。
Male Sprague‐Dawley rats and male B6C3F1 mice excreted 5–15% of a tracer dose of [14C]trichloroethylene as14CO2within 24 h after ip injection of a single dose in a corn‐oil vehicle. The proportion of the dose excreted as CO2was greater in mice than in rats, but increased in the rats after starvation or pretreatment with phenobarbital. As the dose was increased toward the LD50 level, the proportion excreted as14CO2decreased slightly, but this was largely due to increased loss of unchanged trichloroethylene. The excretion of14CO2was thus correlated with the expected level of microsomal metabolism of trichloroethylene to an electrophilic intermediate capable of binding to glutathione or macromolecules. Liver protein labeling was observed to be relatively high (10,000–23,000 cpm/mg in the mouse), while DNA labeling was consistently observed to be very low, not allowing identification of any adducts by high‐performance liquid chromatography (HPLC). Also, no effect on DNA fragmentation was seen by alkaline sucrose gradient centrifugation after injection of an LD50 dose of trichloroethylene. The ability of trichloroethylene to interact with DNA in vivo was thus observed to be very slight.