Non-linearities in the cellular response to ionizing radiation and the role of p53 therein.

Non-linearities in the cellular response to ionizing radiation and the role of p53 therein. Int J Radiat Biol. 2020 Jan 27;:1-42 Authors: Murray D, Mirzayans R Abstract Many aspects of the cellular response to agents such as ionizing radiation that cause genotoxic and/or oxidative stress exhibit a non-linear relationship to the applied stress level. These include elements of the antioxidant response and of the damage-signaling pathways that determine cell fate decisions. The wild-type p53 protein, which is mutated in many cancers, coordinates these responses and is a key determinant of this non-linearity. Indeed, p53 has been referred to as a "cellular rheostat" that favors antioxidant/cytoprotective functions at low stress levels while switching to a pro-oxidant/cytotoxic role under high-stress conditions. For solid tumor-derived cell lines, moderate doses of radiation, typical of those used to generate clonogenic survival curves (i.e., ≤10 Gy), predominantly invoke a dose-dependent cytostatic response. For cancer cell lines with wild-type p53, cytostasis is primarily associated with features of senescence, whereas cancer cells with aberrant p53 primarily undergo endopolyploidization and enlargement. In line with a commentary by Meyn and colleagues [Int J Radiat Biol. 2009, 85:107-115] concluding that apoptosis is not the primary cause of radiation-induced loss of clonogenicity in solid tumor-derived cell lines, significant leve...
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research