Abstract
We have investigated genomic instability in normal human fibroblasts induced by low fluences of different types of radiation, such as gamma rays, neutrons and high-LET heavy ions, focusing on the radiation-quality dependence in both cell-killing effects and mutation induction. The cells were pre-treated with low-fluence irradiation (~1mGy/7-8h) of 137Cs gamma rays, 241Am-Be neutrons, helium (LET=2.3keV/μm), carbon (LET=13.3keV/μm) and iron ions (LET=200keV/μm) before following irradiation with an X-ray challenge dose (1.5Gy). No difference was observed in cell-killing effects, which was detected with the colony-forming assay for reproductive cell death, using pre-treatment with different types of radiations. For mutation induction at hprt locus detected as 6-thioguanine resistant clones, there was no difference in X-ray-induced mutation frequency at 1.5Gy of X-ray challenge dose between un-pretreated and gamma-ray pre-treated cells. In the case of the pre-treatment with heavy ions, mutation frequency was around 4.0 times higher in carbon-ion pre-treated cells and 1.9 times higher in helium-ion pre-treated cells than that in un-pretreated cell. However, X-ray-induced mutation frequency in cells pre-treated with helium and carbon ions was reduced at the control level, when using a specific inhibitor of gap-junction mediated cell-cell communication (40μM lindane). There is evidence that gap-junction mediated cell-cell communication play an important role of inducing genomic instability by pre-treatment with heavy ions.
