Frei E, Frank N, Wiessler M
German Cancer Research Center, Institute for Toxicology and Chemotherapy, Heidelberg.
J Cancer Res Clin Oncol. 1990;116(6):569-74. doi: 10.1007/BF01637076.
Some of the target organs for nitrosamine carcinogenicity have a low activating capacity but many carcinogenic nitrosamines can be activated in the liver. Conjugates, such as phosphates, are chemically accessible reaction products of 1-OH-nitrosamines, and are either potential detoxication products or potential transport forms for activated nitrosamines. 14C-labeled 1-(N-ethyl-N-nitrosamino)ethyl phosphate was tested for its ability to enter primary rat hepatocytes but no uptake was detectable. No uptake was observable into fibroblasts and human leukocytes. N-Nitrosomethylbenzylamine is efficiently 1-C-hydroxylated by hepatocytes but the corresponding 1-C-phosphate was detectable neither in the cells nor in the surrounding medium. N-Nitrosamino-1-phosphates, unlike 1-glucuronides, therefore, do not seem to be important for nitrosamine toxicokinetics.
亚硝胺致癌作用的一些靶器官活化能力较低,但许多致癌性亚硝胺可在肝脏中被活化。诸如磷酸盐之类的缀合物是1-羟基亚硝胺的化学可及反应产物,它们要么是潜在的解毒产物,要么是活化亚硝胺的潜在转运形式。对14C标记的1-(N-乙基-N-亚硝基氨基)乙基磷酸盐进入原代大鼠肝细胞的能力进行了测试,但未检测到摄取。在成纤维细胞和人白细胞中未观察到摄取。N-亚硝基甲基苄胺可被肝细胞有效地进行1-C-羟基化,但相应的1-C-磷酸盐在细胞内和周围培养基中均未检测到。因此,与1-葡糖醛酸苷不同,N-亚硝基氨基-1-磷酸盐似乎对亚硝胺的毒代动力学并不重要。