title: Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells.
abstract: Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on γH2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in γ-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration.
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Hofer
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Falk
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Komůrková
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.|Department of Medical Technology, St. Elisabeth University of Health and Social Sciences , Palackého 1, SK-810 00 Bratislava, Slovak Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Falková
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Bačíková
authors.forename: Bořivoj
authors.initials: B
authors.lastname: Klejdus
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Pagáčová
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Štefančíková
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Weiterová
authors.affiliation: Institute of Experimental Botany, v.v.i., Czech Academy of Sciences , Na Karlovce 1, CZ-160 00 Prague 6, Czech Republic.
authors.forename: Karel J
authors.initials: KJ
authors.lastname: Angelis
authors.affiliation: Department of Cell Biology and Radiobiology, Institute of Biophysics, v.v.i., Czech Academy of Sciences , Královopolská 135, CZ-612 65 Brno, Czech Republic.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kozubek
authors.affiliation: Institute of Biostatistics and Analyses, Masaryk University , Kamenice 126/3, CZ-625 00 Brno, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Dušek
authors.affiliation: Department of Medical Technology, St. Elisabeth University of Health and Social Sciences , Palackého 1, SK-810 00 Bratislava, Slovak Republic.
authors.forename: Štefan
authors.initials: Š
authors.lastname: Galbavý
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D004999:Amifostine / Q000493:pharmacokinetics / Q000494:pharmacology*; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells / Q000187:drug effects / Q000528:radiation effects; D008624:Mercaptoethylamines / Q000493:pharmacokinetics; D008856:Microscopy, Fluorescence / Q000379:methods; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D000469:Alkaline Phosphatase; D004999:Amifostine