Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
Biochemistry (Mosc). 2010 Jun;75(6):675-85. doi: 10.1134/s0006297910060015.
This review analyzes the available information concerning mechanisms of non-genotoxic action of reactive oxygen species (ROS) during tumor promotion and pathways of their generation under the influence of chemical compounds. Special attention is given to the ability of ROS to induce pseudohypoxia through inhibition of prolyl oxidase, which is an oxygen sensor in the cell. Functions of HIF-1alpha as a main contributor to the ROS-induced promotion are analyzed. Data suggest that an unregulated high level of HIF-1alpha in the cell could induce the development of tumors. Hypothetical possibilities of ROS production under the influence of different environmental pollutants, which are promoters of tumorigenesis, include functioning of cytochrome P450 during oxidation of substrates, functioning of the mitochondrial respiratory chain, and action of peroxisome proliferators.
这篇综述分析了有关活性氧（ROS）在肿瘤促进过程中非遗传毒性作用机制以及在化合物影响下生成途径的现有信息。特别关注 ROS 通过抑制脯氨酰氧化酶诱导假性缺氧的能力，脯氨酰氧化酶是细胞中的氧气感受器。分析了 HIF-1alpha 作为 ROS 诱导促进作用的主要贡献者的功能。数据表明，细胞中不受调节的高水平 HIF-1alpha 可能会诱导肿瘤的发展。在不同的环境污染物（肿瘤发生的促进剂）的影响下产生 ROS 的假设可能性包括：在底物氧化过程中细胞色素 P450 的功能、线粒体呼吸链的功能和过氧化物酶体增殖物的作用。
