title: Induction of ROS, p53, p21 in DEHP- and MEHP-exposed LNCaP cells-protection by selenium compounds.
abstract: This study was designed to investigate the hypothesis that the toxic effects of di(2-ethylhexyl)phthalate (DEHP), the most abundantly used plasticizer and ubiquitous environmental contaminant that cause alterations in endocrine and spermatogenic functions in animals is mediated through the induction of reactive oxygen species (ROS) and activation of nuclear p53 and p21 proteins in LNCaP human prostate adenocarcinoma cell line. Protective effects of two selenocompounds, sodium selenite (SS) and selenomethionine (SM) were also examined. It was demonstrated that 24 h exposure of the cells to 3 mM DEHP or its main metabolite, mono(2-ethylhexyl)phthalate (MEHP, 3 μM) caused strongly amplified production of ROS. Both SS (30 nM) and SM (10 μM) supplementations reduced ROS production, and p53 and p21 activation that induced significantly only by MEHP-exposure. The overall results of this study indicated that the induction of oxidative stress is one of the important mechanisms underlying the toxicity of DEHP and this is mainly through the effects of the metabolite, MEHP. Generated data also emphasized the critical role of Se in modulation of intracellular redox status, implicating the importance of the appropriate Se status in cellular response against testicular toxicity of phthalates.
authors.affiliation: Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey.
authors.forename: P
authors.initials: P
authors.lastname: Erkekoğlu
authors.forename: W
authors.initials: W
authors.lastname: Rachidi
authors.forename: O G
authors.initials: OG
authors.lastname: Yüzügüllü
authors.forename: B
authors.initials: B
authors.lastname: Giray
authors.forename: M
authors.initials: M
authors.lastname: Oztürk
authors.forename: A
authors.initials: A
authors.lastname: Favier
authors.forename: F
authors.initials: F
authors.lastname: Hıncal
mesh_terms: D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010795:Phthalic Acids / Q000633:toxicity; D010968:Plasticizers / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012645:Selenomethionine / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology*; D013091:Spermatogenesis / Q000187:drug effects; D013733:Testicular Diseases / Q000139:chemically induced / Q000188:drug therapy; D013737:Testis / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010795:Phthalic Acids; D010968:Plasticizers; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C032279:phthalic acid; D012645:Selenomethionine; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; D018038:Sodium Selenite