Toxicology of quinone-thioethers.
Cytotoxicity associated with exposure to quinones has generally been attributed to either redox cycling, and the subsequent development of "oxidative stress," and/or to their interaction with cellular nucleophiles, such as protein and non-protein sulfhydryls. Glutathione (GSH) is the major non-protein sulfhydryl present in cells, and conjugation of potentially toxic electrophiles with GSH is usually associated with detoxication and excretion. However, this review discusses the biological (re)activity of quinone-thioethers. For example, quinone-thioethers are (1) capable of redox cycling (2) substrates for, and inhibitors of, a variety of enzymes (3) methemoglobinemic (4) potent nephrotoxicants (5) DNA reactive and (6) may contribute to quinone-mediated carcinogenicity and neurotoxicity. The ubiquitous nature of quinones, and the high intracellular concentrations of GSH, ensures that cells and tissues will be exposed to quinone-thioethers. The toxicological importance of quinone-thioethers in quinone-mediated toxicities therefore deserves further attention.
Monks
T J
TJ
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712.
Lau
S S
SS
D000818:Animals; D006801:Humans; D010084:Oxidation-Reduction; D011809:Quinones / Q000633:toxicity*; D013440:Sulfides / Q000633:toxicity*
D011809:Quinones; D013440:Sulfides