Nabb Diane L, Mingoia Robert T, Yang Ching-Hui, Han Xing
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714, USA.
Aquat Toxicol. 2006 Oct 25;80(1):52-9. doi: 10.1016/j.aquatox.2006.07.012. Epub 2006 Jul 22.
Biotransformation plays a key role in detoxification, bioactivation and bioaccumulation of xenobiotics in fish. Biotransformation capabilities in fish, however, are not as thoroughly characterized as in mammals. In this study, basal level activities of 7-ethoxyresorufin O-dealkylase (EROD), 7-methoxyresorufin O-dealkylase (MROD), 7-pentoxyresorufin O-dealkylase, chlorzoxazone 6-hydroxylase, testosterone 6beta-hydroxylase, lauric acid 11-hydroxylase, and glutathione S-transferase in freshly isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) and rat were obtained and compared. All the activities, when normalized to cellular protein concentrations, were significantly lower in rainbow trout hepatocytes than those in rat hepatocytes. Rainbow trout cytochrome P450 (CYP) 2B-, 2E1-, and 3A-like activities were respectively 14-, 18.4-, and 11.8-fold lower than rat. The smallest difference between the two species was CYP1A-type activities (EROD and MROD, 3.4- and 3.7-fold lower in rainbow trout, respectively). Our results suggest that the relative importance of CYP1A enzymes (among CYP subfamilies) in the biotransformation of xenobiotics in rainbow trout is likely much greater than that in mammals.
生物转化在鱼类对外源化学物质的解毒、生物活化和生物积累过程中起着关键作用。然而,鱼类的生物转化能力并不像哺乳动物那样得到充分的表征。在本研究中,我们获取并比较了虹鳟(Oncorhynchus mykiss)和大鼠新鲜分离的肝细胞中7-乙氧基异吩恶唑酮O-脱烷基酶(EROD)、7-甲氧基异吩恶唑酮O-脱烷基酶(MROD)、7-戊氧基异吩恶唑酮O-脱烷基酶、氯唑沙宗6-羟化酶、睾酮6β-羟化酶、月桂酸11-羟化酶和谷胱甘肽S-转移酶的基础水平活性。当以细胞蛋白浓度进行标准化时,虹鳟肝细胞中的所有活性均显著低于大鼠肝细胞。虹鳟细胞色素P450(CYP)2B-、2E1-和3A-样活性分别比大鼠低14倍、18.4倍和11.8倍。两种物种之间最小的差异是CYP1A-型活性(EROD和MROD,虹鳟分别低3.4倍和3.7倍)。我们的结果表明,在虹鳟中,CYP1A酶(在CYP亚家族中)在外源化学物质生物转化中的相对重要性可能远大于哺乳动物。