Vascular changes in a human malignant melanoma xenograft following single-dose irradiation

The effects of single-dose irradiation (5.0-25.0 Gy) on the vascular structure, i.e., the vascular network architecture, of a human melanoma grown in athymic nude mice were studied. The vessels were filled with a radio-opaque medium administered via the abdominal aorta of the mice. X-ray images obtained from 720-micron thick tumor sections provided qualitative information on the vascular structure. Vessel length, surface, and volume per unit tumor volume for vessels with diameters in the ranges 5-15, 15-25, 25-35, 35-45, and greater than 45 micron were obtained by stereological analysis on 2-micron thick tumor sections. A considerable fraction of the vessels was severely damaged after irradiation. Manifestation of the damage as a reduction in the number of functional vessels appeared mainly 0.5-1.5 weeks after irradiation. About 35-45% of the original vessels with diameters in the range 5-15 micron was found to be nonfunctional 1 week after doses of 10.0-15.0 Gy while vessels with larger diameters required doses above 15.0 Gy to become nonfunctional 1 week after exposure. Loss of 50% of the functional vessels with diameters in the ranges 5-15, 15-25, and 25-35 micron was found to require doses of about 16, 21, and 20 Gy, respectively. In spite of a considerable early loss of functional vessels, tumors exposed to 20.0 and 25.0 Gy eventually became supervascularized after irradiation due to extensive radiation-induced tumor shrinkage. Regrowth of irradiated tumors appeared to be preceded by neovascularization, and regrowing tumors could even be better vascularized than unirradiated ones, probably as a result of efficient neovascularization.