Comparative metabolism of 2,6-dimethylnitrosomorpholine in rats, hamsters, and guinea pigs.
Comparative metabolism of 2,6-dimethylnitrosomorpholine in rats, hamsters, and guinea pigs.
复制标题
2,6-二甲基亚硝基吗啉在大鼠、仓鼠和豚鼠体内的代谢比较。
作者：
B. Underwood;W. Lijinsky
研究了N-[3，5-3H]亚硝基-2，6-二甲基吗啉(NDMM)在雌性SD大鼠体内的代谢。叙利亚金黄仓鼠和豚鼠。NDMM可诱发大鼠食道肿瘤、仓鼠胰腺癌和豚鼠肝脏血管内皮细胞瘤。NDMM灌胃剂量(2 mg，2MUCI/只)在大鼠和金黄地鼠的组织中迅速分布，在任何一个组织中都没有明显的放射性聚集。在低剂量水平下，NDMM在两个物种中都能迅速代谢。仓鼠似乎比老鼠或豚鼠代谢化合物的速度更快。8小时后，所有三种动物的尿中都有相当数量的放射性排泄：仓鼠的放射性排泄率约为54%，大鼠的放射性排泄率为39%，豚鼠的排出量为30%。在最初的24小时内，仓鼠、大鼠和豚鼠排出的放射性中只有一小部分是NDMM(分别为0.8%、2%和0.5%)。对给药24小时后收集的尿液进行高压液相色谱分析，发现12种代谢物。虽然这三个物种的尿代谢物看起来都很相似，但一个很大的区别是在仓鼠的尿液中存在一种主要的尿代谢物，这种代谢物在大鼠和豚鼠中不存在或只有少量存在。与仓鼠或大鼠相比，豚鼠尿液中的一个主要组分也有相对更多的放射性。
The metabolism of N-[3,5-3H]nitroso-2,6-dimethylmorpholine (NDMM) was studied in female Sprague-Dawley rats. Syrian golden hamsters, and guinea pigs. NDMM induces tumors in the esophagus in rats, pancreatic cancer in hamsters, and hemangioendothelial tumors of the liver in guinea pigs. An intragastric dose of NDMM (2 mg, 2 muCi/animal) was rapidly distributed throughout the tissues of both the rat and hamster, with no apparent accumulation of radioactivity in any one tissue. At low dose levels, NDMM was metabolized rapidly by both species. The hamster appeared to metabolize the compound faster than did the rat or guinea pig. At appreciable amount of radioactivity was excreted in the urine in all three species after 8 hr: approximately 54% in the hamster, 39% in the rat; and 30% in the guinea pig. During the first 24 hr, only a small percentage of the radioactivity excreted by the hamster, rat, and guinea pig was NDMM (0.8, 2, and 0.5%, respectively). High-pressure liquid chromatography analysis of urine collected 24 hr after administration revealed 12 metabolites. Although the urinary metabolites appeared to be similar in all three species, one large difference was the presence of a major urinary metabolite in hamster urine, which was absent or present in only small quantities in the rat and guinea pig. The guinea pig urine also had relatively more radioactivity present in one major fraction than did the hamster or rat.