Fractionated ionizing radiation exposure induces apoptosis through caspase-3 activation and reactive oxygen species generation.
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.
Bucci
Barbara
B
AFAR-Centro Ricerca S. Pietro, Fatebenefratelli Hospital, Via Cassia 600, 00189 Rome, Italy. bucci.barbara@fbfrm.it
Misiti
Silvia
S
Cannizzaro
Annapaola
A
Marchese
Rodolfo
R
Raza
Giorgio H
GH
Miceli
Roberto
R
Stigliano
Antonio
A
Amendola
Donatella
D
Monti
Olimpia
O
Biancolella
Michela
M
Amati
Francesca
F
Novelli
Giuseppe
G
Vecchione
Aldo
A
Brunetti
Ercole
E
De Paula
Ugo
U
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*
D017382:Reactive Oxygen Species; D053148:Caspase 3