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Role of Quinones in Toxicology

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Department of Medicinal Chemistry and Pharmacognosy (M/C 781), College of Pharmacy, The University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612-7231, Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205, Department of Pharmacology, University of Pennsylvania School of Medicine, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104-6084, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, and Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712-1074
Cite this: Chem. Res. Toxicol. 2000, 13, 3, 135–160
Publication Date (Web):February 23, 2000
https://doi.org/10.1021/tx9902082
Copyright © 2000 American Chemical Society

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    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).

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     This review is based on a symposium entitled “Role of Quinones in Toxicology” which was presented at the Society of Toxicology Conference, New Orleans, LA, March 13−16, 1999.

    *

     To whom correspondence should be addressed:  Department of Medicinal Chemistry and Pharmacognosy (M/C 781), College of Pharmacy, The University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612-7231. Fax:  (312) 996-7107. E-mail:  Judy.Bolton@ UIC.edu.

     The University of Illinois at Chicago.

    §

     Johns Hopkins University.

     University of Pennsylvania.

     University of Oklahoma.

    @

     University of Texas at Austin.

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