Nitric Oxide is a Key Molecule Serving as a Bridge between Radiation-Induced Bystander and Adaptive Responses

A classical paradigm of radiation biology asserts “targeted effect” that all radiation effects on cells, tissues and organisms are due to the direct action of radiation. However, over the past two decades, a paradigm of radiation biology has undergone a shift away from “targeted effect” relationships and towards complex ongoing “intra- and inter-cellular responses”, which involve not only targeted but also non-targeted ones. These responses include now familiar, but still fully unknown, phenomena associated with low-dose/low-dose-rate radiation exposure such as adaptive responses, bystander responses, low-dose hypersensitivity, and genomic instability. The mechanisms underlying these responses often involve biochemical/molecular signals that respond to targeted and non-targeted events. Matsumoto et al. have previously found that nitric oxide functions as initiators of radiation-induced bystander and adaptive responses. These findings suggest correlations between the radioadaptive and bystander responses. The present review focuses on these two phenomena by summarizing observations supporting their existence, and discussing the linkage between them from the aspect of production of reactive nitrogen species.