Abstract
Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety of biological systems, including 3D human tissue samples, the mechanism is not known. There is recent evidence that the cyclooxygenase-2 (COX-2) signaling cascade plays an essential role in the bystander process. The observations that heritable DNA alterations can be propagated to cells many generations after radiation exposure and that bystander cells exhibit genomic instability in ways similar to directly hit cells indicate that the low dose radiation response is a complex interplay of various modulating factors. A better mechanistic understanding of cellular and tissue responses to low dose / low dose rate radiation will provide important insights into how radiation induces its effects.
