Brittebo E B, Kowalski B, Ghantous H, Brandt I
Department of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala Biomedical Centre.
Toxicology. 1989 May 31;56(1):35-45. doi: 10.1016/0300-483x(89)90210-2.
The metabolism and binding of 14C-labelled 1,2-dichloroethane (DCE) in female C57BL-mice were studied. As shown by whole-body autoradiography with heated and organic solvent-extracted tissue sections of i.v. injected mice, a selective localization of non-volatile and bound DCE-metabolites occurred in the nasal olfactory mucosa and the tracheo-bronchial epithelium. Low levels of metabolites were also present in the epithelia of the upper alimentary tract, vagina and eyelid, and in the liver and kidney. A decreased mucosal and epithelial binding was observed after pretreatment with metyrapone, indicating that the binding might be due to an oxidative metabolism of DCE. The quantitated levels of in vivo binding were considerably lower in mice injected i.p. with DCE, as compared to mice given equimolar doses of 14C-labelled 1,2-dibromoethane. In vitro experiments with 1000 g supernatants from various tissues showed that the nasal mucosa has a marked ability to activate DCE into products that become irreversibly bound to the tissue. It is proposed that the nasal olfactory mucosa is a target tissue for toxicity of DCE.
研究了14C标记的1,2 - 二氯乙烷(DCE)在雌性C57BL小鼠体内的代谢和结合情况。通过对静脉注射小鼠的加热及有机溶剂提取的组织切片进行全身放射自显影显示,非挥发性和结合型DCE代谢产物选择性地定位于鼻嗅觉黏膜和气管 - 支气管上皮。上消化道、阴道和眼睑的上皮以及肝脏和肾脏中也存在低水平的代谢产物。用甲吡酮预处理后观察到黏膜和上皮结合减少,表明这种结合可能是由于DCE的氧化代谢所致。与腹腔注射等摩尔剂量14C标记的1,2 - 二溴乙烷的小鼠相比,腹腔注射DCE的小鼠体内结合的定量水平要低得多。用来自各种组织的1000g上清液进行的体外实验表明,鼻黏膜具有将DCE激活为与组织不可逆结合产物的显著能力。有人提出鼻嗅觉黏膜是DCE毒性的靶组织。