ABSTRACT
BACKGROUND: Recent results implicate nitric oxide (NO) in the irradiation-induced perturbation of angiogenic mechanisms. We have previously shown, using the chick embryo chorioallantoic membrane (CAM) and a dose of 10 Gy, that the NO pathway is involved in X-ray-induced anti-angiogenicity. In the current study, we investigated the implication of NO in the effects of various doses (2-15 Gy) of irradiation on angiogenesis. MATERIALS AND METHODS: X-irradiation, NO synthase inhibitors, NO releasing agent and the in vivo CAM angiogenesis model (disc and ring method) were used. The CAM areas were irradiated on the 9th or the 14th day of embryo development and the vascular density was determined morphologically. RESULTS: Doses up to 5 Gy resulted in dose-dependent reduction of vascular density, whereas the NO synthase inhibitors, added immediately post-irradiation, protected the 9-day CAM from the above anti-angiogenic effects of irradiation. NO donor, under certain circumstances potentiated the effects of X-rays when applied to the 9-day CAM using the ring method. CONCLUSION: These results confirm the implication of NO in the anti-angiogenic mechanism of X-rays and describe the dose-response pattern of NO involvement in this action.
Subject(s)
Neovascularization, Physiologic/radiation effects , Nitric Oxide Donors/pharmacology , Nitric Oxide/physiology , Animals , Arginine/pharmacology , Chick Embryo , Chorioallantoic Membrane/blood supply , Chorioallantoic Membrane/drug effects , Dose-Response Relationship, Radiation , Enzyme Inhibitors/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Neovascularization, Physiologic/drug effects , Neovascularization, Physiologic/physiology , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitroarginine/pharmacology , Nitroprusside/pharmacology , X-RaysABSTRACT
PURPOSE: To investigate the combined effects of paclitaxel and single or fractionated doses of ionizing radiation on the angiogenesis process, using as a model the chick embryo choriallantoic membrane (CAM). MATERIAL AND METHODS: Experiments were performed on 9-day CAM, when membranes were irradiated with various single or fractionated doses of X-rays, either alone or in combination with paclitaxel (6.4 micro g/disk). RESULTS: Single doses of irradiation (5, 10, or 15 Gy) produced a significant antiangiogenic effect, which was not dose-dependent. Fractionated doses of X-rays (two doses of 2.5, 5, or 7.5 Gy, each 12 h apart) exerted a dose-dependent reduction of the vascular density index. Paclitaxel was not shown to provoke radiosensitization in this model, i. e., to inhibit angiogenesis of the 9-day CAM. CONCLUSION: These data confirm that the CAM system can be conveniently and properly used for radiobiological studies and indicate that paclitaxel in combination with ionizing radiation does not inhibit further angiogenesis in the system used.
