Metabolism of the hamster pancreatic carcinogen methyl-2-oxopropylnitrosamme by hamster liver and pancreas
Metabolism of the hamster pancreatic carcinogen methyl-2-oxopropylnitrosamme by hamster liver and pancreas
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DOI：
10.1385/ijgc:27:2:105
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发表时间：
2000-04-01
期刊：
影响因子：
--
通讯作者：
Mirvish, SS
中科院分区：
文献类型：
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作者：
Chen, SC;Wang, XJ;Mirvish, SS
背景, 甲基-2-氧代亚硝胺 (MOP) 被激活的机制仍不清楚, 为了开始研究这一机制, 我们在与叙利亚仓鼠和大鼠的肝脏和胰腺切片以及匀浆一起孵育期间跟踪 MOP 的消失,方法, 孵育后, 100 μM MOP 的消失和代谢物的出现通过高效液相色谱 (HPLC) 和紫外线 (UV) 检测进行跟踪, 结果, 消失率为 1,2仓鼠肝脏切片的 nmol/mg 蛋白质/h；仓鼠胰腺切片、导管和腺泡为零；航空大鼠肝脏和胰腺切片；仓鼠肝脏匀浆和细胞溶胶以及仓鼠胰腺匀浆和微粒体分别为 11.8、12.8、1.3 和 2.3 nmol MOP/mg/h。主要的 MOP 代谢物通过其 HPLC 行为及其 H-1-NMR 和质谱鉴定为甲基-2-羟丙基亚硝胺 (MHP)，MHP 产率通常与 MOP 消耗量相似，但对于 MOP 消耗量为零仓鼠胰腺匀浆尽管能够代谢MOB，结论，MOP在仓鼠中是一种胰腺致癌物，但在大鼠中则不然，在代谢研究中，仓鼠肝切片和匀浆（特别是细胞质）从MOP产生MHP，这可能是一种失活反应，仓鼠胰腺匀浆（特别是微粒体部分），但不是大鼠胰腺匀浆，代谢MOP而不形成MHP，表明另一种代谢途径，也许激活会产生近端致癌物。
Background, The mechanism whereby methyl-2-oxoprspylnitrosamine (MOP) is activated remains unknown, To begin investigating this mechanism, we followed MOP disappearance during its incubation with liver and pancreatic slices and homogenates from Syrian hamsters and rats,Methods, after the incubations, disappearance of 100 mu M MOP and appearance of a metabolite was followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection,Results, Disappearance rates were 1,2 nmol/mg protein/h for hamster liver slices; zero for hamster pancreatic slices, ducts and acini; aero for rat liver and pancreatic slices; and 11.8, 12.8, 1.3, and 2.3 nmol MOP/mg/h for hamster liver homogenate and cytosol, and hamster pancreas homogenate and microsomes, respectively, The principal MOP metabolite was identified as methyl-2-hydroxypropylnitrosamine (MHP) by its HPLC behavior and its H-1-NMR and mass spectra, MHP yields were generally similar to MOP consumption, but were zero for hamster pancreatic homogenate despite its ability to metabolize MOB,Conclusion, MOP is a pancreatic carcinogen in hamsters but not in rats, In metabolic studies, hamster liver slices and homogenate (especially the cytosol) produced MHP from MOP, This is probably an inactivation reaction, Hamster pancreas homogenate (especially the microsome fraction), but not rat pancreas homogenate, metabolized MOP without forming MHP, indicating another route metabolism, perhaps activation to give the proximal carcinogen.