Tumor suppressor p53 response is blunted by low-dose-rate radiation

INTRODUCTION Modulation of gene expression in response to ionizing radiation is of prime interest in the field of radiation biology. In most articles concerning biological responses to ionizing radiation, the findings of radiation-induced gene expression after irradiation at a lethal dose range (2-50 Gy) has been reported. Recently, the biological effect of low dose radiation on cellular responses has received attention because protection against low dose radiation less than 1 Gy may be required as a factor of life circumstance. Although epidemiological data regarding the cancer incidence from areas with high background radiation levels seem to favor a beneficial effect of chronic low dose radiation, the molecular mechanisms remain unclear. It has been considered that p53 is not only a guardian of the genome but also an integrator of stress-response signals [1]. The p53 gene exerts various biological functions through transactivation of downstream genes including WAF1. The p53 gene plays important roles in maintaining genomic stability as a cell cycle checkpoint in G1 and G2/M transition and an effector of DNA repair or apoptosis. We previously reported that p53 accumulation was induced in several organs of whole body-irradiated mice and rats receiving less than 0.5 Gy [2,3], and that preirradiation of the cells with chronic γ-rays at a low dose rate blunted the response of p53 and WAF1 in response to challenge with acute irradiation in cultured human glioblastoma cells [4]. In the present study, to examine whether chronic irradiation at a low dose rate induces WAF1 expression in a different manner from acute irradiation, we analyzed the cellular content of p53 and WAF1 after various schedules of irradiation in cultured human glioblastoma cells.