Studies of bystander effects in human fibroblasts using a charged particle microbeam

Purpose: To determine the role of cell-to-cell mediated effects in the response of cells to different radiations by using a charged particle microbcam capable of targeting individual cells with counted particles. Materials and methods: Primary human fibroblasts were irradiated conventionally with X-rays or alpha-particles and scored for the induction of micronucleated or apoptotic cell formation at various times after irradiation. Cells were also individually irradiated with helium-3 particles from a microbeam and the distribution of damaged cells between hit and non-hit cells scored. Results: Conventionally exposed fibroblasts showed a dose-dependent production of micronucleated and apoptotic cells 3 days after irradiation for both X-rays and alpha-particles, with a high RBE value for alpha-particles at low doses. Targeting individual alpha-particles, using a microbeam, to four cells within a population produced more micronucleated and apoptotic cells than expected on the basis of a direct effect only. Conclusions: This study provides direct evidence for the production of transmissible, cell-to-cell effects between hit and non-hit cells individually exposed to charged particles.