Cytoplasmic and nuclear toxicity of 3,5-dimethylaminophenol and potential protection by selenocompounds.

Pinar Erkekoglu, Ming-Wei Chao, Wenjie Ye, Jing Ge, Laura J Trudel, Paul L Skipper, Belma Kocer-Gumusel, Bevin P Engelward, Gerald N Wogan, Steven R Tannenbaum

Index: Food Chem. Toxicol. 72 , 98-110, (2014)

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Abstract

Most common alkylanilines in the environment are 2,6-dimethylaniline (2,6-DMA), 3,5-dimethylaniline (3,5-DMA), and 3-ethylaniline (3-EA). 3,5-Dimethylaminophenol (3,5-DMAP), a metabolite of 3,5-DMA, is of particular interest, as it is potentially genotoxic. Supplementation with organic or inorganic forms of selenium (Se) may reduce toxicity following exposure to a wide variety of environmental chemicals. This study was designed to evaluate the protective effects of sodium selenite (SS) and selenomethionine (SM) at varying time points of supplementation (24 h and 72 h) against the cytotoxicity, reactive oxygen species (ROS) production, and genotoxicity of 3,5-DMAP in CHO AS52 cells. 3,5-DMAP caused dose-dependent increase of cytotoxicity, ROS production and genotoxicity, and generated free radicals in the nuclei. Thioredoxin reductase (TrxR), catalase and glutathione reductase activities, and glutathione levels were significantly lower while lipid peroxidation and protein oxidation levels were higher after 3,5-DMAP treatment in both cytoplasm and the nucleus vs. control. After 24 h, both SS and SM provided protection in antioxidant/oxidant status of the 3,5-DMAP-treated cells; however other than supplying higher glutathione peroxidase and TrxR activities, 72 h supplementation did not provide advanced improvement. Selenocompounds may be beneficial against cytotoxic and genotoxic potential of 3,5-DMAP and might protect both nucleus and cytoplasm following exposure to alkylanilines.Copyright © 2014 Elsevier Ltd. All rights reserved.