Abstract
Phosphorylated ATM immunofluorescent staining was used to investigate the dose-response relationship for the number of DNA double strand breaks induced in non-dividing primary normal human fibroblasts cells irradiated with doses from 1.2 mGy to 100 mGy. The induction of DNA double strand breaks showed a supralinear dose-response relationship; the number of breaks per unit dose in the range of 1.2-5 mGy exceeded that at higher doses. Radiation-induced bystander effects, which can enhance cell damage, may explain these findings. To test this hypothesis, the number of DNA double strand breaks in cells treated with lindane, an inhibitor of radiation-induced bystander effects, prior to X-ray irradiation was assessed; a supralinear dose-response relationship was not observed. Moreover, the number of DNA double strand breaks obtained by subtracting the number of phosphorylated ATM foci in lindane-treated cells from the number of phosphorylated ATM foci in untreated cells was proportional to the dose at low doses (1.2-5 mGy) and was saturated at doses from 10-100 mGy. Thus, the increase in the number of DNA double strand breaks per unit dose in the range of 1.2-5 mGy was largely due to radiation-induced bystander effects, while at doses >10 mGy, the DNA double strand breaks might be induced mainly by dose-dependent direct radiation effects and partly by dose-independent radiation-induced bystander effects. The findings of our present study provide a direct evidence of the dose-response relationship for radiation-induced bystander effects from broad X-rays not microbeam.
