Induction of ROS, p53, p21 in DEHP- and MEHP-exposed LNCaP cells-protection by selenium compounds


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ERKEKOĞLU Ü. P. , Rachidi W., Yüzügüllü O., Giray B., Öztürk M., Favier A., ...More

Food and Chemical Toxicology, vol.49, no.7, pp.1565-1571, 2011 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 49 Issue: 7
  • Publication Date: 2011
  • Doi Number: 10.1016/j.fct.2011.04.001
  • Journal Name: Food and Chemical Toxicology
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.1565-1571
  • Keywords: DEHP, MEHP, p53, p21, ROS, Selenium, OXIDATIVE STRESS, DI(2-ETHYLHEXYL) PHTHALATE, DNA-DAMAGE, PEROXISOME PROLIFERATORS, DIETHYLHEXYL PHTHALATE, CANCER PREVENTION, GENE-EXPRESSION, IN-VITRO, APOPTOSIS, MECHANISMS

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. © 2011 Elsevier Ltd.