Host: The Japan Radiation Research Society
Because biological response to ionizing radiation is dependent on time or dose rate, irradiation with a same dose gives rise to different biological response at different dose rate or for different irradiation time. We have observed dose rate effect in micronucleus formation and growth inhibition of human cell lines, in which the effects are exponentially declined as the dose rate is decreased, and have proposed a new dose rate effect model named MOE model through the statistical analysis of the data. In this paper, we studied property of human cell lines exposed to low dose rate for long period more than five month. A human osteosarcoma, U2OS, and a human glioma, M059K, were continuously exposed to gamma-ray in an irradiation room bearing 50,000 Ci cobalt-60. Growth inhibition is equilibrated to depend on dose-rate after the several month continuous irradiation. Minimum inhibitory dose-rate for the growth inhibition was about 50 mGy/h. Cell cycle analysis demonstrated G1 arrest in the cells continuously exposed to low dose rate gamma-ray, while G2 arrest in the cells acutely exposed to high dose rate gamma-ray. Cells continuously exposed to low dose rate gamma ray exhibited delayed growth suppression even after one month culture under background environment, and kept high level expression of c-Jun and its phosphorylations at serine 63 and 73, whereas high level expression of p53 and its phosphorylations at serine 15 and 20 was returned to the normal levels. M059K cells continuously exposed to low dose rate radiation were resistant to apoptosis caused by staurosporine and chemotherapeutic agents. These results suggest that AP-1 activation is involved in delayed growth suppression induced by continuous low dose rate irradiation, and that optimization of irradiation schedule is crucial for radiation cancer therapy.
