Bystander effect induced by counted high-LET particles in confluent human fibroblasts; A Mechanistic study

Shao, C.*; Furusawa, Yoshiya*; Kobayashi, Yasuhiko; Funayama, Tomoo; Wada, Seiichi

The possible mechanism of a radiation-induced bystander response was investigated by using a high-LET heavy particle microbeam, which allows selected cells to be individually hit with precise numbered particles. Even when only a single cell within the confluent culture was hit by one particle of Ar40 or Ne20, a 1.4-fold increase of micronuclei (MN) was detected demonstrating a bystander response. When 49 cells in the culture were individually hit by 1 to 4 particles, the production of MN in the irradiated cultures were about 2-fold higher than control levels but independent of the number and LET of the particles. MN induction in the irradiated-culture was partly reduced by treatment with DMSO, a scavenger of reactive oxygen species (ROS), and it was almost fully suppressed by the mixture of DMSO and PMA, an inhibitor of gap junctional intercellular communication (GJIC). Accordingly, both ROS and GJIC contribute to the above-mentioned bystander response and GJIC might play an essential role by mediating the release of soluble biochemical factors from targeted cells.