Ionizing radiation: the good, the bad, and the ugly

Abstract

Skin changes caused by ionizing radiation have been scientifically documented since 1902. Ionizing radiation is a widely accepted form of treatment for various types of cancer. Despite the technological advances, radiation skin injury remains a significant problem. This injury, often referred to as radiation dermatitis, occurs in about 95% of patients receiving radiation therapy for cancer, and ranges in severity from mild erythema to moist desquamation and ulceration. Ionizing radiation is not only a concern for cancer patients, but also a public health concern because of the potential for and reality of a nuclear and/or radiological event. Recently, the United States has increased efforts to develop medical countermeasures to protect against radiation toxicities from acts of bioterrorism, as well as cancer treatment. Management of radiation dermatitis would improve the therapeutic benefit of radiation therapy for cancer and potentially the mortality expected in any "dirty bomb" attack. Currently, there is no effective treatment to prevent or mitigate radiation skin injury. This review summarizes "the good, the bad, and the ugly" of current and evolving knowledge regarding mechanisms of and treatments for radiation skin injury.

Figure 1. Schematic identifying the key cells and mediators involved in radiation skin injury

Ionizing radiation incites signaling between the epidermis and dermis through resident skin cells. In the epidermis, immediate damage to the basal keratinocytes and burst of free radicals, result in the increased formation of various cytokines and chemokines, most notably IL-1α, IL-1β, TNFα, IL-6, IL-8, CCL4, CXCL10, and CCL2. Keratinocytes, along with fibroblasts and endothelial cells in the dermis, stimulate resident skin cells and recruit circulating immune cells, such as neutrophils and macrophages. Additionally, langerhans cells in the epidermis and dendritic cells in the dermis migrate to lymph nodes for antigen presentation and immune cell stimulation. Degranulation of mast cells release derived histamine, serotonin, TNFα, and tryptase. Fibroblast stimulation is involved in acute, late, and healing of radiation skin injury Oxidative stress is generated at the time of radiation exposure, as well as days after irradiation due to propagation of free radicals and inflammatory cell recruitment, creates and antioxidant imbalance. RNS = reactive nitrogen species; ROS = reactive oxygen species; bFGF = basic fibroblast growth factor; EGF = epidermal growth factor; KGF = keratinocyte growth factor.