Radioprotection

Cell, tissue and organ specific pathways of ionizing irradiation toxicity. Subtotal lung irradiation is shown as an example. Single alveolar pneumoncytes from an area within lung tissue are shown relative to total lung irradiation. Individual cells experience ionizing irradiation-induced production of radical oxygen species (ROS) including superoxide, hydroxyl radical, nitric oxide and peroxynitrite from the interaction of ionizing irradiation with oxygen and water. ROS interaction with pyrimidine and purine bases nuclear DNA produces single and double strand breaks, initiation of DNA repair, communication of DNA damage through the cell cytoplasm to the mitochondrial membrane via (stress activated protein (SAP) kinases) and then translation of pro-apoptotic, BCL2 family members from nucleus to mitochondria (86). Then follows mitochondrial membrane permeability, cytochrome c disassociation from cardiolipin, and cytoplasmic leakage of cytochrome c which leads to activation of the caspase-3 pathway and apoptosis (17-18, 86). Both dying and irradiated but recovering cells release ROS and inflammatory cytokines including IL-1, TNFα and TGFβ, which directly (through cell to cell contact with other cells in the tissue), and indirectly (via the circulation to cells at distant sites), produce acute local tissue and systemic effects respectively. Within the irradiated tissue differences in radiosensitivity of different cell phenotypes (endothelial cells, alveolar pneumocytes, alveolar macrophages and bronchopulmonary stem cells) contribute to the magnitude of tissue damage. The volume of tissue within the lung that is in the irradiation beam determines as does irradiation dose the magnitude of acute and chronic normal tissue effects.