Macromolecular binding and metabolism of the carcinogen 1,2-dibromoethane.
Macromolecular binding and metabolism of the carcinogen 1,2-dibromoethane.
复制标题
致癌物 1,2-二溴乙烷的大分子结合和代谢。
作者：
D. L. Hill;T. Shih;T. Johnston;R. Struck
摘要对致癌物1，2-二溴乙烷的作用、活化和失活机制进行了生物化学研究。[1，2 - 14 C]-1，2-二溴乙烷的可测量放射性量与大鼠所有主要组织的蛋白质、RNA和DNA结合。对于这些类别的大分子中的每一种，最大量的结合放射性在肝脏和肾脏中。以1，2-二溴乙烷为底物，建立了大鼠肝谷胱甘肽S-转移酶的最适反应条件.最适pH为8.2，1，2-二溴乙烷的Km为25 mm，Vmax为2.1 µ mol/min/g肝脏。在大鼠肾脏中发现相当大的酶活性;在肺、睾丸、脾和心脏中存在可检测的活性。在大鼠肝微粒体中存在导致[14 C]-1，2-二溴乙烷放射性与反应系统中蛋白质不可逆结合的酶活性。该活性可被苯巴比妥诱导，但不被苯并[a]蒽诱导。还原型烟酰胺腺嘌呤二核苷酸磷酸是非诱导型和诱导型反应的活性所必需的; MgCl 2刺激了这两种反应。溴乙醛是一种可能参与不可逆结合的反应性化合物，被鉴定为反应体系中形成的代谢产物。[14 C]-1，2-二溴乙烷的放射性也通过非酶化学反应与微粒体蛋白结合。导致与大分子结合的酶促反应和/或化学结合反应可能涉及1，2-二溴乙烷的生物活性。
Abstract Biochemical investigations relating to mechanisms of action, activation, and inactivation have been made on the carcinogen, 1,2-dibromoethane. Measurable amounts of radioactivity from [1,2- 14 C]-1,2-dibromoethane became bound to protein, RNA, and DNA of all major tissues of rats. For each of these classes of macromolecules, the largest amounts of bound radioactivity were in the liver and kidneys. Optimum conditions for the rat liver glutathione S -transferase that utilizes 1,2-dibromoethane as a substrate have been established. The pH optimum was 8.2, the K m for 1,2-dibromoethane was 25 mm, and the V max was 2.1 µmol/min/g liver. Considerable enzyme activity was found in rat kidney; detectable activity was present in lung, testis, spleen, and heart. Enzymatic activity leading to the irreversible binding of radioactivity from [ 14 C]-1,2-dibromoethane to proteins in the reaction system was present in rat liver microsomes. The activity was inducible by phenobarbital but not by benz[ a ]anthracene. Reduced nicotinamide adenine dinucleotide phosphate was required for activity of both the noninduced and the induced reactions; MgCl 2 stimulated both reactions. Bromoacetaldehyde, a reactive compound probably involved in the irreversible binding, was identified as a metabolite formed in the reaction system. Radioactivity from [ 14 C]-1,2-dibromoethane also became bound to microsomal proteins by a nonenzymatic chemical reaction. The enzymatic reaction leading to binding to macromolecules and/or the chemical binding reaction may be involved in the biological activity of 1,2-dibromoethane.