Dose and dose rate effects of low dose ionizing radiation on activation of p53 in immortalized murine cells

Abstract

We examined the biological effects of low dose rate (LDR) of 60Co γ-ray irradiation (from 0.1–10 cGy/h) on the transcriptional activity of p53, using NIH/PG13Luc cells stably transfected with p53-dependent luciferase reporter plasmid. Microarray analysis revealed up-regulations of six P53-mediated genes (CDKN1A/p21, MDM2, SIP27, CCNG1/cyclin G1, EI24/PIG8 and Dinb/POLK) by exposure of cells for 72 h to LDR 60Co γ-ray irradiation. Using a real-time PCR, a significant elevation in the expression of CCNG1/cyclin G1, MDM2 and CDKN1A/p21 was observed at dose rates over 5 cGy/h. The dose rate dependency of these three p53-mediated genes was also observed. The expression of CCNG1/cyclin G1 at high dose rates (HDRs) γ-rays was higher than that for LDR. However, the expression of MDM2 for LDR γ-rays was higher than for HDR. Cells irradiated with γ-rays at 0.1 and 1 cGy/h appeared to show G1 phase arrest. Furthermore, G2 growth arrest was observed in cells irradiated with γ-rays at 5 and 10 cGy/h, being correlated with p53-mediated CCNG1/cyclin G1 up-regulation. These results imply that cellular response to radiation differs between the two LDRs used, 0.1–1 cGy/h and over 5 cGy/h.