Role of quinones in toxicology
Role of quinones in toxicology
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DOI：
10.1021/tx9902082
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发表时间：
2000-03-01
影响因子：
4.1
通讯作者：
Monks, TJ
中科院分区：
文献类型：
--
作者：
Bolton, JL;Trush, MA;Monks, TJ
喹酮类化合物是一类毒理中间体，可在体内产生多种有害效应，包括急性细胞毒性、免疫毒性和致癌作用。对苯二酚引起这些影响的机制可能相当复杂。喹诺酮类化合物是迈克尔受体，细胞损伤可通过关键细胞蛋白和/或DNA的烷基化发生。另外，对苯二酚是一种高度氧化还原活性的分子，可以与它们的半喹酮自由基进行氧化还原循环，从而导致活性氧物种(ROS)的形成，包括超氧化物、过氧化氢，并最终产生羟基自由基。ROS的产生可通过形成氧化的细胞大分子，包括脂质、蛋白质和DNA，在细胞内造成严重的氧化应激。氧化损伤碱基的形成，如8-氧脱氧鸟苷，与衰老和致癌有关。此外，ROS还可以激活许多信号通路，包括蛋白激酶C和RAS。本文以苯、多环芳烃、雌激素和儿茶酚胺为例，探讨了苯醌的多种细胞毒性作用。这些证据有力地表明，苯醌毒性的众多机制(即烷基化和氧化应激)可以与已知的母体化合物(S)的病理相关。
Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael accepters, and cellular damage can occur through alkylation of crucial cellular proteins and/or DNA. Alternatively; quinones are highly redox active molecules which can redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can cause severe oxidative stress within cells through the formation of oxidized cellular macromolecules, including lipids, proteins, and DNA. Formation of oxidatively damaged bases such as 8-oxodeoxyguanosine has been associated with aging and carcinogenesis. Furthermore, ROS can activate a number of signaling pathways, including protein kinase C and RAS. This review explores the varied cytotoxic effects of quinones using specific examples, including quinones produced from benzene, polycyclic aromatic hydrocarbons, estrogens, and catecholamines. The evidence strongly suggests that the numerous mechanisms of quinone toxicity (i.e., alkylation vs oxidative stress) can be correlated with the known pathology of the parent compound(s).