Gap junction communication and the propagation of bystander effects induced by microbeam irradiation in human fibroblast cultures; The Impact of radiation quality

Autsavapromporn, N.*; Suzuki, Masao*; Funayama, Tomoo; Usami, Noriko*; Plante, I.*; Yokota, Yuichiro; Muto, Yasuko*; Ikeda, Hiroko; Kobayashi, Katsumi*; Kobayashi, Yasuhiko; Uchihori, Yukio*; Hei, T. K.*; Azzam, E.*; Murakami, Takeshi*

We investigated the role of gapjunction intercellular communication (GJIC) in the propagation of stressful effects in confluent normal human fibroblast cultures wherein only 0.036-0.144% of cells in the population were traversed by primary radiation tracks. Confluent cells were exposed to graded doses from X ray, carbon ion, neon ion or argon ion microbeams in the presence or absence of an inhibitor of GJIC. After 4 h incubation, the cells were assayed for micronucleus (MN) formation. Micronuclei were induced in a greater fraction of cells than expected based on the fraction of cells targeted by primary radiation, and the effect occurred in a dose-dependent manner with any of the radiation sources. Interestingly, the inhibition of GJIC depressed the enhancement of MN formation in bystander cells from cultures exposed to high-LET radiation but not low-LET radiation. The results highlight the important role of radiation quality and dose in the observed effects.