Quinones as mutagens, carcinogens, and anticancer agents: introduction and overview.
Quinones as mutagens, carcinogens, and anticancer agents: introduction and overview.
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醌作为诱变剂、致癌剂和抗癌剂：介绍和概述。
DOI：
10.1080/15287398509530776
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Smith,MT
中科院分区：
文献类型：
--
作者：
Smith,MT
喹酮类化合物广泛存在于我们的环境中，既有天然存在的，也有作为污染物存在的。因此，人类对它们的接触是广泛的。喹酮类化合物还形成一类重要的有毒代谢物，由苯酚和相关化合物的代谢产生，包括苯酚本身、1-萘酚和二乙基己烯甾醇。对苯二酚产生毒性作用的机制很复杂，但似乎主要涉及两个过程：硫基的直接芳基化反应和通过氧化还原循环产生的活性氧物种。已证明某些苯醌通过形成活性氧物种而致突变，而另一些则通过转化为DNA结合的半喹酮自由基而致突变。矛盾的是，对苯二酚不仅具有诱变性，因此具有潜在的致癌性，而且还是有效的抗癌剂。经典的例子是阿霉素(盐酸阿霉素)和丝裂霉素C，但其他较不复杂的醌也显示出有效的抗肿瘤活性。设计对人类肿瘤细胞的毒性更具选择性并了解其作用机制的新型醌类化合物似乎是治疗癌症的一种有前途的方法，特别是如果可以通过使用化学保护剂来防止宿主毒性的话。
Quinones are widespread in our environment, occurring both naturally and as pollutants. Human exposure to them is therefore extensive. Quinones also form an important class of toxic metabolites generated as a result of the metabolism of phenols and related compounds, including phenol itself, 1‐naphthol, and diethyl‐stilbesterol. The mechanisms by which quinones exert their toxic effects are complex, but two processes appear to be centrally involved: the direct arylation of sulfhydryls, and the generation of active oxygen species via redox cycling. Certain quinones have been shown to be mutagenic via the formation of active oxygen species and others via their conversion to DNA‐binding semiquinone free radicals. Paradoxically, quinones are not only mutagenic and therefore potentially carcinogenic, they are also effective anticancer agents. Classic examples are Adriamycin (doxorubicin hydrochloride) and mitomycin C, but other less complex quinones also show effective antitumor activity. The design of novel quinones that are more selective in their toxicity to human tumor cells and whose mechanism of action is understood seems a promising approach in cancer treatment, especially if host toxicity can be prevented via the use of chemoprotective agents.