title: Transient delay of radiation-induced apoptosis by phorbol acetate.
abstract: The mechanisms of interference of a model tumour promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) with radiation-induced apoptosis in human peripheral lymphocytes have been investigated. The cells were treated with TPA under various conditions and thereafter exposed to a single lethal dose of gamma radiation. Morphological and biochemical changes characteristic of apoptosis were followed up to 72 h of post-irradiation time. Acute exposure to low concentration of TPA resulted in delay in the onset of radiation-induced apoptosis (determined as morphological changes and rate of mitochondrial demise) by 24-48 h as compared to the irradiated, sham TPA-treated cells. The time course of this delay correlated well with confinement of the p53 protein to the cytoplasm and increase in bcl-2 levels at the nuclear periphery of irradiated cells. Our results indicate that confinement of p53 in the cytoplasm is one of the potential mechanisms by which TPA interferes with the process of radiation-induced apoptosis in human lymphocytes.
authors.affiliation: Department of Molecular Biosciences, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, 106 91, Stockholm, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olsson
authors.affiliation: Department of Molecular Biosciences, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, 106 91, Stockholm, Sweden. Stefan.Czene@su.se.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0002-7606-4911
authors.initials: S
authors.lastname: Czene
authors.affiliation: Department of Molecular Biosciences, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, 106 91, Stockholm, Sweden.
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
authors.affiliation: Department of Molecular Biosciences, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, 106 91, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Harms-Ringdahl
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D013755:Tetradecanoylphorbol Acetate
keywords: 12-O-tetra-decanoylphorbol-13-acetate; Apoptosis; Human lymphocytes; Mitochondria; Radiation; bcl-2; p53