Wang C Y, Imaida K, Zukowski K, Lee M S
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Cancer Lett. 1991 Feb;56(2):153-7. doi: 10.1016/0304-3835(91)90090-5.
The role of 2-aminofluorene and its N-glucuronide and the O-glucuronide of N-hydroxy-2-acetylaminofluorene in the bladder carcinogenesis by 2-aminofluorene were investigated. These compounds were injected into heterotopically transplanted bladders of male rats at a weekly dose of 1 mumol for 20 weeks. The experiment was terminated at the end of 50 weeks. The results showed that none of these compounds were carcinogenic in the heterotopically transplanted bladder. The O-glucuronide was not carcinogenic even when it was administered in a phosphate saline (pH 8.0), that favors the activation of this compound. The N-glucuronide of N-hydroxy-2-aminofluorene, a positive control, produced urothelial tumors. These results are consistent with the hypothesis that the N-glucuronides of hydroxylamines, but not the O-glucuronides of hydroxamic acids, are responsible for bladder carcinogenesis by arylamines.
研究了2-氨基芴及其N-葡糖醛酸苷和N-羟基-2-乙酰氨基芴的O-葡糖醛酸苷在2-氨基芴诱发膀胱致癌作用中的角色。将这些化合物以每周1 μmol的剂量注射到雄性大鼠异位移植的膀胱中，持续20周。实验在50周结束时终止。结果显示，这些化合物在异位移植的膀胱中均无致癌性。即使将O-葡糖醛酸苷在有利于该化合物活化的磷酸盐缓冲液（pH 8.0）中给药，它也不具有致癌性。作为阳性对照的N-羟基-2-氨基芴的N-葡糖醛酸苷产生了尿路上皮肿瘤。这些结果与以下假设一致，即羟胺的N-葡糖醛酸苷而非异羟肟酸的O-葡糖醛酸苷是芳基胺诱发膀胱致癌的原因。
