Erkekoglu Pinar, Chao Ming-Wei, Ye Wenjie, Ge Jing, Trudel Laura J, Skipper Paul L, Kocer-Gumusel Belma, Engelward Bevin P, Wogan Gerald N, Tannenbaum Steven R
Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey.
Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Bioscience and Technology, Chung Yuan Christian University, Chungli City, Taoyuan 32023, Taiwan.
Food Chem Toxicol. 2014 Oct;72:98-110. doi: 10.1016/j.fct.2014.06.031. Epub 2014 Jul 9.
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.
环境中最常见的烷基苯胺是2,6 - 二甲基苯胺（2,6 - DMA）、3,5 - 二甲基苯胺（3,5 - DMA）和3 - 乙基苯胺（3 - EA）。3,5 - 二甲基氨基酚（3,5 - DMAP）是3,5 - DMA的一种代谢产物，因其具有潜在的遗传毒性而备受关注。补充有机或无机形式的硒（Se）可能会降低接触多种环境化学物质后的毒性。本研究旨在评估亚硒酸钠（SS）和硒代蛋氨酸（SM）在不同补充时间点（24小时和72小时）对3,5 - DMAP在CHO AS52细胞中的细胞毒性、活性氧（ROS）产生和遗传毒性的保护作用。3,5 - DMAP导致细胞毒性、ROS产生和遗传毒性呈剂量依赖性增加，并在细胞核中产生自由基。与对照组相比，3,5 - DMAP处理后细胞质和细胞核中的硫氧还蛋白还原酶（TrxR）、过氧化氢酶和谷胱甘肽还原酶活性以及谷胱甘肽水平显著降低，而脂质过氧化和蛋白质氧化水平则更高。24小时后，SS和SM均对3,5 - DMAP处理的细胞的抗氧化/氧化状态起到保护作用；然而，除了提供更高的谷胱甘肽过氧化物酶和TrxR活性外，72小时的补充并未带来进一步改善。硒化合物可能对3,5 - DMAP的细胞毒性和遗传毒性具有有益作用，并且在接触烷基苯胺后可能对细胞核和细胞质都起到保护作用。
