title: Fractionated ionizing radiation exposure induces apoptosis through caspase-3 activation and reactive oxygen species generation.
abstract: BACKGROUND
  Radiation therapy (RT) is a well established therapeutic modality for the treatment of solid tumors. In particular, post-operative RT is considered the standard treatment adjuvant to surgery since its ability to prolong median survival of patients with malignant astrocytoma has been shown; nevertheless the ionizing radiation (IR) treatment fails in a considerable number of astrocytoma patients.
  
  
  METHODS
  Using an ADF human astrocytoma cell line the molecular mechanisms involved in the DNA damage induced by fractionated irradiation (FIR) and single IR treatment have been investigated.
  
  
  RESULTS
  FIR and single IR treatment inhibited the growth of the ADF human astrocytoma cell line. FACS analysis revealed that FIR treatment, but not single IR treatment, induced growth inhibition associated with the induction of apoptosis. Apoptosis was related to caspase-3 activation and reactive oxygen species (ROS) generation. ROS formation depends on the up-regulation of the cytochrome P450 enzyme gene. On the contrary, 12.5 Gy induced necrotic cell death up-regulating the HSPD1, HSPCB, HSPCA and HSPB1 genes.
  
  
  CONCLUSIONS
  FIR treatment induced cell death through caspase-3 and ROS-mediated apoptosis.
authors.affiliation: AFAR-Centro Ricerca S. Pietro, Fatebenefratelli Hospital, Via Cassia 600, 00189 Rome, Italy. bucci.barbara@fbfrm.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Bucci
authors.forename: Silvia
authors.initials: S
authors.lastname: Misiti
authors.forename: Annapaola
authors.initials: A
authors.lastname: Cannizzaro
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Marchese
authors.forename: Giorgio H
authors.initials: GH
authors.lastname: Raza
authors.forename: Roberto
authors.initials: R
authors.lastname: Miceli
authors.forename: Antonio
authors.initials: A
authors.lastname: Stigliano
authors.forename: Donatella
authors.initials: D
authors.lastname: Amendola
authors.forename: Olimpia
authors.initials: O
authors.lastname: Monti
authors.forename: Michela
authors.initials: M
authors.lastname: Biancolella
authors.forename: Francesca
authors.initials: F
authors.lastname: Amati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Aldo
authors.initials: A
authors.lastname: Vecchione
authors.forename: Ercole
authors.initials: E
authors.lastname: Brunetti
authors.forename: Ugo
authors.initials: U
authors.lastname: De Paula
mesh_terms: D017209:Apoptosis; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D004789:Enzyme Activation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D053148:Caspase 3