Microvessel density and endothelial cell proliferation after amifostine (Ethyol) administration in vivo

As amifostine is rapidly metabolised by the membrane-bound and capillary alkaline phosphatase to the active metabolite WR-1065, microvessel density in normal and cancer tissue may influence the therapeutic potential of the pro-drug WR-2721. Thus, it is of interest how the administration of amifostine itself alters vascular density.

For this study fertilized eggs were used and 0.05 ml amifostine (25.7 micrograms) was injected into the area vasculosa. As controls untreated area vasculosa were examined as well as eggs treated with 0.05 ml NaCl 0.9%, 48 hr after injection the vascular density was determined by histometrical methods. Applying the LAB method we performed immunohistochemical analysis of the proliferating cell nuclear antigen of endothelial cells.

There was a significant (p < 0.001) difference in vascular density with a mean microvessel count of 25.08 (+/- 8.45 SD) vascular intersections/mm2 in the untreated control, 30.40 (+/- 12.84 SD) in the NaCl control and 53.69 (+/- 24.56 SD) in the amifostine treated area. There was also a significant (p < 0.001) difference in endothelial cell proliferation (PCNA) between untreated controls with a mean PCNA positivity of 14.05 (+/- 5.28 SD) and amifostine treated area vasculosa with a mean PCNA positivity of 32.22 (+/- 18.14 SD).

A single dose administration of 25.7 micrograms amifostine induces endothelial cell proliferation and subsequent neovascularisation in the area vasculosa of the fertilised egg.