Antioxidants and selenocompounds inhibit 3,5-dimethylaminophenol toxicity to human urothelial cells

  • Pinar Erkekoglu Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara
  • Ming-Wei Chao Department of BioScience Technology, College of Science, Chung Yuan Christian University, Zhongli district, Taoyuan city
  • Chia-Yi Tseng Department of Biomedical Engineering, College of Engineering, Chung Yuan Christian University, Zhongli district, Taoyuan city
  • Bevin P. Engelward Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA
  • Ozge Kose Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara
  • Belma Kocer-Gumusel Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara
  • Gerald N. Wogan Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA
  • Steven R. Tannenbaum Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA
Keywords: alkyl anilines, cytotoxicity, genotoxicity, reactive oxygen species, selenium, sodium selenite, selenomethionine

Abstract

Exposure to alkyl anilines may lead to bladder cancer, which is the second most frequent cancer of the urogenital tract. 3,5-dimethylaniline is highly used in industry. Studies on its primary metabolite 3,5-dimethylaminophenol (3,5-DMAP) showed that this compound causes oxidative stress, changes antioxidant enzyme activities, and leads to death of different mammalian cells. However, there is no in vitro study to show the direct effects of 3,5-DMAP on human bladder and urothelial cells. Selenocompounds are suggested to decrease oxidative stress caused by some chemicals, and selenium supplementation was shown to reduce the risk of bladder cancer. The main aim of this study was to investigate whether selenocompounds organic selenomethionine (SM, 10 µmol/L) or inorganic sodium selenite (SS, 30 nmol/L] could reduce oxidative stress, DNA damage, and apoptosis in UROtsa cells exposed to 3,5-DMAP. 3,5-DMAP caused a dose-dependent increase in intracellular generation of reactive oxygen species, and its dose of 50 µmol/L caused lipid peroxidation, protein oxidation, and changes in antioxidant enzyme activities in different cellular fractions. The comet assay also showed single-strand DNA breaks induced by the 3,5-DMAP dose of 50 µmol/L, but no changes in double-strand DNA breaks. Apoptosis was also triggered. Both selenocompounds provided partial protection against the cellular toxicity of 3,5-DMAP. Low selenium status along with exposure to alkyl anilines can be a major factor in the development of bladder cancer. More mechanistic studies are needed to specify the role of selenium in bladder cancer.

Published
2019-02-25
How to Cite
1.
Erkekoglu P, Chao M-W, Tseng C-Y, Engelward BP, Kose O, Kocer-Gumusel B, Wogan GN, Tannenbaum SR. Antioxidants and selenocompounds inhibit 3,5-dimethylaminophenol toxicity to human urothelial cells. Arh Hig Rada Toksikol [Internet]. 2019Feb.25 [cited 2019Oct.23];70(1). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/978
Section
Original article

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