Radiation-induced bystander effects and stress-induced mutagenesis

Abstract

Two very exciting scientific revolutions have occurred in biology in the last 20 or so years. For many years, the world believed that mutations occur at random. The discovery of stress-induced mutagenesis has changed ideas about mutation and evolution and revealed mutagenic programs that differ from standard spontaneous mutagenesis in rapidly proliferating cells. In an equally exciting paradigm shift in the seemingly unrelated field of radiation biology, we have uncovered a potential driver for stress-induced mutagenesis: the bystander effect. Stress - induced mutations occur during growth-limiting stress: nutrient stress for bacteria, and radiation damage for bystander effects. Stress-induced mutations can include adaptive mutations that allow survival in the otherwise hostile environment. The stress responses increase mutagenesis specifically when cells are maladapted to their environments, potentially accelerating evolution. Stress-induced mutation mechanisms may provide important models for the genomic instability underlying some cancers and genetic diseases, for rapid adaptation of biota in changed environments, for resistance to chemotherapeutic and antibiotic drugs, for pathogenicity of microbes, and for many other important evolutionary processes. This chapter reviews our knowledge of radiation-induced bystander effects, and how they may contribute to our mechanistic understanding of mutagenesis and adaptive evolution. Implications for disease therapy, protection of species-including humans-from stressors such as radiation, and mechanisms of evolutionary change are discussed.