Raineri R, Hillesund T, Ernst M K, Cavanaugh D M, Poiley J A
J Appl Toxicol. 1983 Aug;3(4):196-202. doi: 10.1002/jat.2550030407.
The mechanism of benzo[a]pyrene (BP) by cultured kidney, liver, small intestine, lung and trachea from male Syrian golden hamsters and Sprague-Dawley rats was compared. The metabolic capacity of intact cell systems was assessed by determining the formation of organic-solvent and water-soluble metabolites, levels of covalent binding and levels of BP metabolites following separation using high-pressure liquid chromatography. Hepatocytes from both species metabolized three to four times more BP than the other cells studied. Formation of water-soluble metabolites by hepatocytes was at least 10 times that of the other cell types. Generally, hamster cells had greater metabolic capability than rat cells. Levels of covalent binding of metabolites of BP were at least 10 times greater in hepatocytes (uninduced) from both species than in the other cell types. Binding to hepatocytes and hamster embryo cells increased with incubation time coinciding with an increase in the formation of water-soluble and diol metabolites. High levels of water-soluble metabolites accompanied high levels of covalent, whole-cell binding. Hamster embryo cells are transformed by BP without an exogenous metabolic activation system. The presence of hamster and rat hepatocytes inhibited transformation of hamster embryo cells by BP. This inhibition of transformation correlated with the increased rate of formation of water-soluble detoxification metabolites by hepatocytes from both species. The high rate of formation of water-soluble products by intact hepatocytes reflects the in vivo activity of liver cells. Use of hepatocytes in short-term tests allows a system for carcinogen metabolism more closely representing that which is present in the whole animal.
比较了苯并[a]芘（BP）对雄性叙利亚金仓鼠和斯普拉格-道利大鼠的培养肾、肝、小肠、肺和气管的作用机制。通过测定有机溶剂和水溶性代谢产物的形成、共价结合水平以及使用高压液相色谱分离后BP代谢产物的水平，评估完整细胞系统的代谢能力。两种物种的肝细胞代谢BP的量比所研究的其他细胞高三到四倍。肝细胞形成的水溶性代谢产物至少是其他细胞类型的10倍。一般来说，仓鼠细胞的代谢能力比大鼠细胞更强。两种物种未诱导的肝细胞中BP代谢产物的共价结合水平至少比其他细胞类型高10倍。与水溶性和二醇代谢产物形成增加一致，随着孵育时间的延长，与肝细胞和仓鼠胚胎细胞的结合增加。高水平的水溶性代谢产物伴随着高水平的共价、全细胞结合。仓鼠胚胎细胞在没有外源性代谢激活系统的情况下可被BP转化。仓鼠和大鼠肝细胞的存在抑制了BP对仓鼠胚胎细胞的转化。这种转化抑制与两种物种肝细胞形成水溶性解毒代谢产物的速率增加相关。完整肝细胞形成水溶性产物的高速率反映了肝细胞在体内的活性。在短期试验中使用肝细胞可以建立一个更能代表全动物体内致癌物代谢情况的系统。
