Abstract
The observation of radiation-induced bystander responses, where cells respond to their neighbors being irradiated, indicates that the cancer risk of a low dose radiation may be greater than the predicted and it also indicates an opportunity to modulate the efficacy of radiotherapy. Growing evidence indicates that gap junctional intercellular communication (GJIC) plays an important role in the bystander responses. By irradiating a fraction of cells within a primary human fibroblasts population with either low doses of broad heavy ion beams or high-LET heavy ion microbeams, we found that the yields of radiation induced micronucleus (MN) and G1-phase arrest increased when the GJIC was enhanced by 8-Br-cAMP, but they were diminished when the cells were treated with DMSO and they were even eliminated when this GJIC was inhibited by PMA or lindane. Accordingly, both ROS and GJIC contribute to the bystander response in the confluent fibroblasts but the GJIC might play an essential role. With respect to tumor cells, however, the enhanced GJIC reduced radiation-induced cell responses of MN induction and G2-phase arrest, indicating that GJIC does not contribute to the bystander cellular damage. In fact, we found that some radiation-induced soluble factors including nitric oxide and their downstream products such as TGF-beta 1 were the bystander signaling molecules which could induce chromosome damage not only in the non-targeted tumor cells but also in their neighboring fibroblasts.
