Ionizing radiations and collagen metabolism: from oxygen free radicals to radio-induced late fibrosis

Skin fibrosis is one of the most common late adverse effects observed after radiation therapy for cancer. As a dose-limiting factor and hence a major hindrance to increase the amount of radiation delivered to the tumor, this problem can be addressed according to the very early steps of the fibrotic process: the oxygen free radical production. Reactive oxygen species (ROS) generated during radiotherapy result from both inflammatory response and water radiolysis. Many studies have demonstrated that the extracellular matrix molecules are potential targets for ROS, and that collagen metabolism and properties are deeply and permanently modified after irradiation, both in vitro and in vivo. It is therefore possible to design different therapeutic approaches such as the clinical use of liposomal superoxide dismutase able to reverse the imbalance between collagen matrix synthesis and degradation. Finally, the so-called oxidative stress induced by radiation represents a significant parameter leading to fibrosis and will undoubtedly serve to design further experimental and clinical studies.