Wildenauer D B, Oehlmann C E
Biochem Pharmacol. 1982 Nov 15;31(22):3535-41. doi: 10.1016/0006-2952(82)90572-x.
Cyclophosphamide metabolites have been generated in vitro by microsomal oxidation of cyclophosphamide and their binding to rabbit liver microsomes and to intact human red blood cells has been investigated. Reactions with proteins of membrane and cytoplasm were detected by SDS polyacrylamide gel electrophoresis. The protein bands were analysed for incorporation of radioactivity. The following results were obtained. (1) Preferential binding of acrolein to microsomes and erythrocytes, with only little binding of metabolites containing the chloroethyl moiety. (2) Reduction of acrolein binding by the thiol compounds glutathione, 2,3-dimercaptopropane-1-sulfonate and mercaptoethane sulfonate. (3) In microsomes: formation of protein polymerisation products and incorporation of radioactivity. (4) In red blood cells: cross-linking of membrane proteins and formation of globin dimerization products in the cytoplasm.
环磷酰胺代谢产物已通过环磷酰胺的微粒体氧化在体外生成，并且已经研究了它们与兔肝微粒体以及完整人红细胞的结合情况。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳检测与膜蛋白和细胞质蛋白的反应。分析蛋白条带中的放射性掺入情况。获得了以下结果。（1）丙烯醛优先与微粒体和红细胞结合，而含氯乙基部分的代谢产物结合较少。（2）硫醇化合物谷胱甘肽、2,3-二巯基丙烷-1-磺酸盐和巯基乙烷磺酸盐可减少丙烯醛的结合。（3）在微粒体中：形成蛋白质聚合产物并掺入放射性。（4）在红细胞中：膜蛋白交联并在细胞质中形成珠蛋白二聚体产物。
