Cytotoxicity of Air Pollutant 9,10-Phenanthrenequinone: Role of Reactive Oxygen Species and Redox Signaling

Abstract

Atmospheric pollution has been a principal topic recently in the scientific and political community due to its role and impact on human and ecological health. 9,10-phenanthrenequinone (9,10-PQ) is a quinone molecule found in air pollution abundantly in the diesel exhaust particles (DEP). This compound has studied extensively and has been shown to develop cytotoxic effects both in vitro and in vivo. 9, 10-PQ has been proposed to play a critical role in the development of cytotoxicity via generation of reactive oxygen species (ROS) through redox cycling. This compound also reduces expression of glutathione (GSH), which is critical in Phase II detoxification reactions. Understanding the underlying cellular mechanisms involved in cytotoxicity can allow for the development of therapeutics designed to target specific molecules significantly involved in the 9,10-PQ-induced ROS toxicity. This review highlights the developments in the understanding of the cytotoxic effects of 9, 10-PQ with special emphasis on the possible mechanisms involved.

Figure 1

9-10-phenanthrenequinone structure.

Figure 2

Redox cycling of 9,10-phenanthrenequinone (9,10-PQ) for production of reactive oxygen species (ROS). First, 9,10-PQ quinone undergoes 1 electron reduction to produce semiquinone radical. Semiquinone is unstable and is very reactive to oxygen. It reoxidizes back to quinone and releases superoxide radical. Superoxide molecule is then reduced to hydrogen peroxide by the superoxide dismutase. Hydroxyl radicals are formed when hydrogen peroxide reacts with metals such as ferrous ions via Fenton reaction. Second, semiquinone can also undergo further 1 electron reduction to form 9,10-phenanthrene hydroquinone which can further redox cycles back to semiquinone by losing an electron and yielding superoxide radical. Lastly, 2-electron reduction of 9,10-PQ quinone by NADPH-quinone oxidoreductase-1 (NQO1) will directly form 9,10-phenanthrene hydroquinone. Thus, redox cycle of 9,10-PQ will generate a large amount of ROS.