Radiation and the microenvironment – tumorigenesis and therapy

Exposure to ionizing radiation increases the risk of developing cancer at low doses and is used to control cancer at high doses. Ionizing radiation can elicit an 'activated' phenotype in some cells that promotes rapid and persistent remodelling of the extracellular matrix, through the induction of proteases and growth factors, as well as chronic production of reactive oxygen species. The rapid and dynamic cell biology that occurs in irradiated tissues indicates the existence of a microenvironment-mediated damage-response programme. Some mechanisms of the ionizing radiation-induced microenvironment include chronic inflammation and persistent production of transforming growth factor-β. These cellular and tissue responses to ionizing radiation can have non-targetted effects on non-irradiated cells, such as induction of genomic instability and neoplastic progression. The functional consequences of exposing an organism to ionizing radiation are a product of DNA damage, cell loss and altered tissue microenvironments that promote carcinogenesis and might affect responses to anticancer therapies.