Amifostine (WR-2721) is an inorganic thiophosphate-cytoprotective agent 
developed to selectively protect normal tissues against the toxicity of 
chemotherapy and radiation. We have previously shown that amifostine protects 
both chicken embryo chorioallantoic membrane (CAM) vessels and cells from the 
effects of X-rays. In the present work, we studied the effect of amifostine on 
angiogenesis in vivo, using the CAM model. Amifostine decreased the number of 
CAM vessels in a dose-dependent manner, without being toxic for the tissue. It 
also decreased the mRNA levels of both vascular endothelial growth factor (VEGF) 
isoforms VEGF(165) and VEGF(190), 6 and up to 48 h after its application onto 
the CAM. Similarly, it decreased the mRNA levels of inducible nitric-oxide 
synthase, 24 and 48 h after drug application. Furthermore, amifostine decreased 
the deposited amounts of laminin and collagen I 24 h after its application, 
without affecting the expression of the corresponding genes. The protein amounts 
and activity of matrix metalloproteinase-2 were not affected, whereas the 
expression of the corresponding gene was decreased up to 48 h after drug 
application. Finally, the activity of plasmin was increased 6 h after amifostine 
application and remained increased at later time points. These findings suggest 
that amifostine alters the expression of several molecules implicated in the 
angiogenesis process and affects the composition of the extracellular matrix in 
a way that leads to inhibition of angiogenesis. Such an antiangiogenic action of 
amifostine, together with its radioprotective effects, further supports its use 
in combination with radiotherapy for increased therapeutic efficacy.