Role of quinones in toxicology

Judy L. Bolton, Michael A. Trush, Trevor M. Penning, Glenn Dryhurst, Terrence J. Monks

Research output: Contribution to journalReview article

1219 Scopus citations

Abstract

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 acceptors, 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).

Original languageEnglish (US)
Pages (from-to)135-160
Number of pages26
JournalChemical Research in Toxicology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2000

ASJC Scopus subject areas

  • Toxicology

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    Bolton, J. L., Trush, M. A., Penning, T. M., Dryhurst, G., & Monks, T. J. (2000). Role of quinones in toxicology. Chemical Research in Toxicology, 13(3), 135-160. https://doi.org/10.1021/tx9902082