De Long M J, Santamaria A B, Talalay P
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Carcinogenesis. 1987 Oct;8(10):1549-53. doi: 10.1093/carcin/8.10.1549.
NAD(P)H:Quinone oxidoreductase (QR) is a widely-distributed enzyme that promotes obligatory two-electron reductions of quinones and thereby protects cells against the cytotoxicity of quinones and their metabolic precursors. QR is induced by a wide variety of chemoprotectors in many animal tissues as well as in the Hepa 1c1c7 murine hepatoma cell line. Such inducers fall into two families: dual inducers (e.g. polycyclic aromatics, azo dyes, beta-naphthoflavone) that elevate QR as well as cytochrome P1-450, and selective inducers of QR (e.g. tert-butylhydroquinone and other redox-labile diphenols). Induction by the first family of inducers depends on binding to the Ah (Aryl hydrocarbon) receptor and the associated expression of a functional cytochrome P1-450 enzyme, whereas the induction by redox-labile diphenols does not appear to be receptor-mediated. In order to analyze the possible role of the cytochrome P1-450 system in the induction of QR, we examined this process in the Hepa 1c1c7 cells and in four mutants of this cell line that are defective in the induction or expression of functional cytochrome P1-450. tert-Butylhydroquinone was an effective inducer of QR in all of the cell lines, and this process does not, therefore, depend on a functional cytochrome P1-450 enzyme. In contrast, azo dyes and polycyclic aromatics induce QR in the parent cell line but not in the various types of cytochrome P1-450-defective mutants. We conclude that the Ah receptor and cytochrome P1-450 function are involved in the induction of QR by certain azo dyes and polycyclic aromatics, but not by phenolic antioxidants.
NAD(P)H：醌氧化还原酶（QR）是一种广泛分布的酶，它能促进醌的强制性双电子还原，从而保护细胞免受醌及其代谢前体的细胞毒性。QR在许多动物组织以及Hepa 1c1c7小鼠肝癌细胞系中受到多种化学保护剂的诱导。这类诱导剂分为两个家族：双重诱导剂（如多环芳烃、偶氮染料、β-萘黄酮），它们能同时提高QR和细胞色素P1-450的水平；以及QR的选择性诱导剂（如叔丁基对苯二酚和其他氧化还原不稳定的二酚）。第一类诱导剂的诱导作用取决于与芳烃（Ah）受体的结合以及功能性细胞色素P1-450酶的相关表达，而氧化还原不稳定二酚的诱导作用似乎不是受体介导的。为了分析细胞色素P1-450系统在QR诱导中的可能作用，我们在Hepa 1c1c7细胞以及该细胞系的四个在功能性细胞色素P1-450的诱导或表达方面存在缺陷的突变体中研究了这一过程。叔丁基对苯二酚在所有细胞系中都是QR的有效诱导剂，因此，这一过程不依赖于功能性细胞色素P1-450酶。相比之下，偶氮染料和多环芳烃在亲本细胞系中能诱导QR，但在各种类型的细胞色素P1-450缺陷突变体中则不能。我们得出结论，Ah受体和细胞色素P1-450的功能参与了某些偶氮染料和多环芳烃对QR的诱导，但酚类抗氧化剂则不然。
