Role of quinones in toxicology

Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immun otoxicity, 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 DN A. Alternatively; quinones are highly redox active molecules which can redo x cycle with their semiquinone radicals, leading to formation of reactive o xygen species (ROS), including superoxide, hydrogen peroxide, and ultimatel y the hydroxyl radical. Production of ROS can cause severe oxidative stress within cells through the formation of oxidized cellular macromolecules, in cluding lipids, proteins, and DNA. Formation of oxidatively damaged bases s uch as 8-oxodeoxyguanosine has been associated with aging and carcinogenesi s. 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 benz ene, polycyclic aromatic hydrocarbons, estrogens, and catecholamines. The e vidence strongly suggests that the numerous mechanisms of quinone toxicity (i.e., alkylation vs oxidative stress) can be correlated with the known pat hology of the parent compound(s).