Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic.
Chem Res Toxicol. 2013 Feb 18;26(2):290-9. doi: 10.1021/tx3004533. Epub 2013 Jan 15.
Sudan I (1-phenylazo-2-hydroxynaphthol) is a suspected human carcinogen causing tumors in the livers and urinary bladders of rats, mice, and rabbits. Here, we investigated for the first time the influence of Sudan I exposure on the expression of several biotransformation enzymes in the livers, kidneys, and lungs of rats concomitantly at the mRNA and protein levels and assayed their enzymatic activities. We also studied its effect on the formation of Sudan I-derived DNA adducts in vitro. Sudan I increased the total amounts of cytochrome P450 (P450) in all organs tested. Western blots using antibodies raised against various P450s, NADPH:P450 reductase, and NAD(P)H:quinone oxidoreductase 1 (NQO1) showed that the expression of P450 1A1 and NQO1 was induced in the liver, kidney, and lung of rats treated with Sudan I. The higher protein levels correlated with increased enzyme activities of P450 1A1/2 and NQO1. Furthermore, 9.9-, 5.9-, and 2.8-fold increases in the formation of Sudan I oxidative metabolites catalyzed by microsomes isolated from the liver, kidney, and lung, respectively, of rats treated with Sudan I were found. The relative amounts of P450 1A and NQO1 mRNA, measured by real-time polymerase chain reaction (RT-PCR) analysis, demonstrated that Sudan I induced the expression of P450 1A1 and NQO1 mRNA in the liver, kidney, and lung, and of P450 1A2 mRNA in kidney and lung. Finally, microsomes isolated from livers, kidneys, and lungs of Sudan I exposed rats more effectively catalyzed the formation of Sudan I-DNA adducts than microsomes from organs of control rats. This was attributable to the higher P450 1A1 expression. Because P450 1A1 is playing a major role in the bioactivation of Sudan I in rat and human systems, its induction by Sudan I may have a profound effect on cancer risk by this azo dye. In addition, the induction of P450 1A1/2 and NQO1 enzymes can influence individual human susceptibility to other environmental carcinogens and have an effect on cancer risk.
苏丹红 I（1-偶氮-2-羟基萘）是一种疑似人类致癌物，可导致大鼠、小鼠和兔子的肝脏和膀胱肿瘤。在这里，我们首次研究了苏丹红 I 暴露对大鼠肝脏、肾脏和肺部中几种生物转化酶的 mRNA 和蛋白质水平表达的影响，并检测了它们的酶活性。我们还研究了它对体外苏丹红 I 衍生 DNA 加合物形成的影响。苏丹红 I 增加了所有测试器官中的细胞色素 P450（P450）总量。使用针对各种 P450、NADPH：P450 还原酶和 NAD（P）H：醌氧化还原酶 1（NQO1）的抗体进行的 Western 印迹显示，用苏丹 I 处理的大鼠肝脏、肾脏和肺中 P450 1A1 和 NQO1 的表达被诱导。较高的蛋白水平与 P450 1A1/2 和 NQO1 酶活性的增加相关。此外，还发现用苏丹 I 处理的大鼠肝脏、肾脏和肺分离的微粒体分别催化苏丹 I 氧化代谢物形成的 9.9、5.9 和 2.8 倍增加。通过实时聚合酶链反应（RT-PCR）分析测量的 P450 1A 和 NQO1 mRNA 的相对量表明，苏丹 I 诱导了大鼠肝脏、肾脏和肺中 P450 1A1 和 NQO1 mRNA 的表达，以及肾脏和肺中 P450 1A2 mRNA 的表达。最后，苏丹红 I 暴露大鼠肝脏、肾脏和肺分离的微粒体比对照大鼠器官分离的微粒体更有效地催化苏丹 I-DNA 加合物的形成。这归因于 P450 1A1 的表达增加。由于 P450 1A1 在大鼠和人体系统中苏丹 I 的生物活化中起主要作用，因此苏丹 I 对其的诱导可能对该偶氮染料的致癌风险产生深远影响。此外，P450 1A1/2 和 NQO1 酶的诱导可以影响个体对其他环境致癌物的易感性，并对癌症风险产生影响。
