title: Cytoplasmic and nuclear toxicity of 3,5-dimethylaminophenol and potential protection by selenocompounds.
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.
authors.affiliation: 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. Electronic address: erkekp@yahoo.com.
authors.forename: Pinar
authors.initials: P
authors.lastname: Erkekoglu
authors.affiliation: 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.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chao
authors.affiliation: Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Trudel
authors.affiliation: Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Skipper
authors.affiliation: Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey.
authors.forename: Belma
authors.initials: B
authors.lastname: Kocer-Gumusel
authors.affiliation: Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Bevin P
authors.initials: BP
authors.lastname: Engelward
authors.affiliation: Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Wogan
authors.affiliation: Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Tannenbaum
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D019587:Dietary Supplements; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012645:Selenomethionine / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D000975:Antioxidants; D017382:Reactive Oxygen Species; C514328:3,5-dimethylaniline; C007766:2,6-xylidine; D012645:Selenomethionine; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione; D018038:Sodium Selenite; C514327:3-ethylaniline
keywords: 3,5-Dimethylaminophenol; Alkylaniline; Cytotoxicity; Genotoxicity; Oxidative stress; Selenium