RAPID DETECTION OF INDUCERS OF ENZYMES THAT PROTECT AGAINST CARCINOGENS
RAPID DETECTION OF INDUCERS OF ENZYMES THAT PROTECT AGAINST CARCINOGENS
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DOI：
10.1073/pnas.89.6.2394
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发表时间：
1992-03-15
影响因子：
11.1
通讯作者：
TALALAY, P
中科院分区：
文献类型：
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作者：
PROCHASKA, HJ;SANTAMARIA, AB;TALALAY, P
膳食结构是人类和实验动物患癌症风险的主要决定因素。饮食中的主要和次要成分可能会增强或抑制恶性肿瘤的发展。许多饮食成分还通过诱导参与异生物质代谢的酶来改变致癌物的代谢，这是调节癌症风险的一种行之有效的机制。我们开发了一种简单的系统，用于快速检测和测量解毒致癌物酶（II 相酶）的诱导，基于对微量滴定板孔中生长的鼠肝癌细胞中醌还原酶 [NAD(P)H:(醌受体) 氧化还原酶，EC 1.6.99.2] 活性的直接测定。对各种常用有机种植蔬菜的提取物进行醌还原酶诱导剂活性调查，发现十字花科植物（尤其是芸苔属植物）是极其丰富的来源。因此，有趣的是，大量食用这些类型的蔬菜与降低人类癌症风险有关。该测定系统还测量毒性，这与所检查的蔬菜提取物中的诱导剂效力无关。通过使用突变肝癌细胞（对某些细胞色素 P-450 酶的调节有缺陷），保护性 II 相酶的选择性（单功能）诱导剂可以与也提高细胞色素 P-450（I 相酶）从而引起致癌物激活风险的（双功能）诱导剂区分开来。因此，该测定系统不仅可以快速检测人类饮食中的抗癌酶诱导剂，还可以阐明储存和加工对诱导剂活性的影响。
Dietary composition is a major determinant of cancer risk in humans and experimental animals. Major and minor components of the diet may enhance or suppress the development of malignancy. Many dietary constituents also modify the metabolism of carcinogens by induction of enzymes involved in xenobiotic metabolism, and this is one well-established mechanism for modulating the risk of cancer. We have developed a simple system for rapid detection and measurement of the induction of enzymes that detoxify carcinogens (phase II enzymes), based on the direct assay of the activity of quinone reductase [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] in murine hepatoma cells grown in micro-titer plate wells. Survey of extracts of a variety of commonly consumed, organically grown vegetables for quinone reductase inducer activity identified crucifers (and particularly those of the genus Brassica) as singularly rich sources. It is therefore of interest that high consumption of these types of vegetables has been correlated with decreased cancer risk in humans. The assay system also measures toxicity, which was unrelated to inducer potency among the vegetable extracts examined. By use of mutant hepatoma cells (defective in regulation of certain cytochrome P-450 enzymes) selective (monofunctional) inducers of protective phase II enzymes can be distinguished from (bifunctional) inducers that also elevate cytochromes P-450 (phase I enzymes) and thereby pose the risk of carcinogen activation. The assay system therefore permits not only rapid detection of inducers of anticarcinogenic enzymes in the human diet but also elucidation of effects of storage and processing on inducer activities.