PARENT SESSION
1:30 PM to 3:30 PM
Sunday, April 21, 2002
Poster Session 7 Radioprotectors
Room: Nevada Exhibition Center
(P12-106) Amifostine induces smad 7 activation in megacaryocytes irradiated in vivo.
Segreto, Roberto1, Ferreira, Alice2, Kimura, Edna3, Franco, Marcello4, Egami, Mizue5, Silva, Maria Regina4, Segreto, Helena*,1, 1 Department of Medicine - Radiotherapy, Sao Paulo, SP2 Department of Biophisics, Sao Paulo, S P3 Department of Histology, Sao Paulo, S P4 Department of Pathology, Sao Paulo, S P5 Department of Morphology, Sao Paulo, S P
ABSTRACT-
The role of amifostine in the activation of TGF beta 1 and in the smad cascade in megakaryocytes ( Meg )irradiated in vivo was assessed using immunohistochemistry. The animals were treated with phisiological saline solution ( PSS ) intraperitoneally (ip )- G1, amifostine ( ip )- G2, PSS ( ip ) + 7Gy of 60Co - G3, and amifostine ( ip ) + 7Gy of 60Co - G4. Animals in G4 showed significantly less reticulin fibrosis and higher bone marrow cellularity compared to G3. Non-irradiated Meg ( G1,G2 ) were negative to active TGFbeta1.Immunopositivity to TGFbeta1 was detected 10 days after irradiation in G3 and G4. At the same period,smad 2/3 and smad 4 were positive in the nucleoli of irradiated Meg ( G3 ) and negative in the nucleoli of Meg irradiated in the presence of amifostine ( G4 ). Smad 7 immunopositivity was detected in the cytoplasm of Meg in amifostine treated bone marrows (G2,G4 ).Amifostine does not prevent TGF beta 1 activation in irradiated Meg, but whilst growth inhibitory and fibrogenic signals occur in the untreated marrows, these signals are inhibited in amifostine treated marrows due to the induction of smad 7 activation.
KEYWORDS: Amifostine, Ionizing radiation, megakaryocytes, smad cascade