Modulation of normal human skin fibroblasts responses to ionizing radiations by gap junction

Understanding the biological effects of different types of ionizing radiation (IR) is essential for cancer therapy. Here, we focused on the role of gap junction intercellular communication (GJIC) modulating the repair of potentially lethal damage (PLDR) and micronuclei formation in cells exposed to low- or high-linear energy transfer (LET) IR, by which every cell is traversed by IR track. Confluent cells were exposed in the presence or absence of gap junction inhibitor to X rays (LET-1.7keV/um), carbon ions (LET-76keV/um), silicon ions (LET-113keV/um) or iron ions (LET-400keV/um) that result in isosurvival levels. They were incubated for various times at 37oC. As expected, high-LET IR were more effective than low-LET IR at inducing of cell killing and DNA damage, shortly after irradiation. However, maintaining cells in the confluent state for various times resulted in PLDR coupled with a reduction in DNA damage, occurred only in cells exposed to low-LET IR, but not in those exposed to high-LET IR. Interestingly, inhibition of GJIC significantly enhanced cell survival and a reduction in DNA damage in cells exposed to high-LET IR but not in low-LET IR. Overall, these results show that LET and GJIC play an important role of the propagation of stressful effects in among irradiated cells exposed to high-LET IR and that GJIC has only minimal effect on PLDR and induction of DNA damage following low-LET IR. This finding opens the new approaches in cancer treatment.日本放射線影響学会第５５回大