title: The antioxidant butylated hydroxyanisole potentiates the toxic effects of propylparaben in cultured mammalian cells.
abstract: Butylated hydroxyanisole and propylparaben are phenolic preservatives commonly used in food, pharmaceutical and personal care products. Both chemicals have been subjected to extensive toxicological studies, due to the growing concern regarding their possible impacts on environmental and human health. However, the cytotoxicity and underlying mechanisms of co-exposure to these compounds have not been explored. In this study, a set of relevant cytotoxicity endpoints including cell viability and proliferation, oxidative stress, DNA damage and gene expression changes were analyzed to assess whether the antioxidant butylated hydroxyanisole could prevent the pro-oxidant effects caused by propylparaben in Vero cells. We demonstrated that binary mixtures of both chemicals induce greater cytotoxic effects than those reported after single exposureto each compound. Simultaneous treatment with butylated hydroxyanisole and propylparaben caused G0/G1 cell cycle arrest as a result of enhanced generation of oxidative stress and DNA double strand breaks. DNA microarray analysis revealed that a cross-talk between transforming growth factor beta (TGFβ) and ataxia-telangiectasia mutated kinase (ATM) pathways regulates the response of Vero cells to the tested compounds in binary mixture. Our findings indicate that butylated hydroxyanisole potentiates the pro-oxidant effects of propylparaben in cultured mammalian cells and provide useful information for their safety assessment.
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Pérez Martín
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Fernández Freire
authors.affiliation: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Ctra. de Colmenar km 9, 28034 Madrid, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Daimiel
authors.affiliation: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Ctra. de Colmenar km 9, 28034 Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Botas
authors.affiliation: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Ctra. de Colmenar km 9, 28034 Madrid, Spain.
authors.forename: Covadonga Martín
authors.initials: CM
authors.lastname: Sánchez
authors.affiliation: Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Ctra. de Colmenar km 9, 28034 Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Lasunción
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Peropadre
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Darwin, 2, 28049 Madrid, Spain. Electronic address: mariajose.hazen@uam.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Hazen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004249:DNA Damage / Q000187:drug effects; D023381:Endpoint Determination; D046228:Microarray Analysis; D018384:Oxidative Stress / Q000187:drug effects; D010226:Parabens / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014709:Vero Cells
chemical_list: D000975:Antioxidants; D010226:Parabens; D017382:Reactive Oxygen Species; D002083:Butylated Hydroxyanisole; C006068:propylparaben
keywords: Binary mixtures; Cell cycle; DNA damage; Gene expression changes; Oxidative stress; Vero cells