Radio-adaptive response of hprt mutation in normal human fibroblasts induced by proton microbeams.

Recently we have investigated that the mutation frequency at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus, which was detected with measuring 6-thioguanine resistant clones, in normal human fibroblasts induced by the 200kVp X-ray challenging dose (1.5Gy) was reduced at 0.15 times in cells pre-treated with low-dose-rate neutrons (1mSv/8h) as a priming dose compared to unpre-treated cells. Furthermore, the reduced mutation frequency was returned to the control level, when using a specific inhibitor of gap-junction mediated cell-cell communication (40µM lindane). We set up a hypothesis that recoiled protons emitted by the interaction between primary neutrons and surroundings near irradiated cells induce radio-adaptive response in irradiated cell population via gap-junction mediated bystander effect. To examine the hypothesis around 1.5% of total cells were irradiated with single 3.4MeV proton before irradiating the X-ray challenging dose using the microbeam irradiation system, Single Particle Irradiation system to Cell (SPICE) in National Institute of Radiological Sciences, Japan. The result clearly showed that the X-ray induced mutation frequency of hprt locus was suppressed in cells pre-treated with proton microbeams and returned to the control level, when using a specific inhibitor of gap-junction mediated cell-cell communication. The result suggests that neutron-induced adaptive response is caused by recoiled protons and gap-junction mediated bystander effect plays an important role to induce such cellular response.56th Annual Meeting of Radiation Research Societ