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

摘要

We examined the biological effects of low dose rate (LDR) of ~(60)Co/-ray irradiation (from 0.1 to 10 cGy/h) on the transcriptional activity of p53, using MH/PG13Luc cells stably transfected with p53-dependent luciferase reporter plasmid. Microarray analysis revealed up-regulations of six P53-mediated genes (CDKNlA/p21, MDM2, SIP27, CCNGl/cyclin Gl, EI24/PIG8 and Dinb/ POLK) by exposure of cells for 72 h to LDR ~(60)Co 7-ray irradiation. Using a real-time PCR, a significant elevation in the expression of CCNGl/cyclin Gl, MDM2 and CDKNlA/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 CCNGl/cyclin Gl at high dose rates (HDRs) 7-rays was higher than that for LDR. However, the expression of MDM2 for LDR 7-rays was higher than for HDR. Cells irradiated with 7-rays at 0.1 and 1 cGy/h appeared to show Gl phase arrest. Furthermore, G2 growth arrest was observed in cells irradiated with 7-rays at 5 and 10 cGy/h, being correlated with p53-mediated CCNGl/cyclin Gl 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.