Relationship between p53 status and the bioeffect of ionizing radiation (Review)

Abstract

Radiotherapy is widely used in the clinical treatment of cancer patients and it may be used alone or in combination with surgery or chemotherapy to inhibit tumor development. However, radiotherapy may at times not kill all cancer cells completely, as certain cells may develop radioresistance that counteracts the effects of radiation. The emergence of radioresistance is associated with the genetic background and epigenetic regulation of cells. p53 is an important tumor suppressor gene that is expressed at low levels in cells. However, when cells are subjected to stress-induced stimulation, the expression level of p53 increases, thereby preventing genomic disruption. This mechanism has important roles in maintaining cell stability and inhibiting carcinogenesis. However, mutation and deletion destroy the anticancer function of p53 and may induce carcinogenesis. In tumor radiotherapy, the status of p53 expression in cancer cells has a close relationship with radiotherapeutic efficacy. Therefore, understanding how p53 expression affects the cellular response to radiation is of great significance for solving the problem of radioresistance and improving radiotherapeutic outcomes. For the present review, the literature was searched for studies published between 1979 and 2021 using the PubMed database ( ) with the following key words: Wild-type p53, mutant-type p53, long non-coding RNA, microRNA, gene mutation, radioresistance and radiosensitivity. From the relevant studies retrieved, the association between different p53 mutants and cellular radiosensitivity, as well as the molecular mechanisms of p53 affecting the radiosensitivity of cells, were summarized. The aim of the present study was to provide useful information for understanding and resolving radioresistance, to help clinical researchers develop more accurate treatment strategies and to improve radiotherapeutic outcomes for cancer patients with p53 mutations.

Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin

“…Several studies have defined P53 as a key molecule involved in radioresponse of cells, since it is linked to radiotherapy efficacy, [50][51][52] and is considered as a biomarker for clinical radiosensitivity. 53 Radiation-induced expression of P53 has been demonstrated in glioblastoma and hepatocellular carcinoma cells, 54,55 similar to our results that indicated upregulation of P53 by 7-geranyloxycoumarin and radiation. Hence, observed combinatorial effects in present study could also be explained by changes induced in the expression of BMI-1, NF-κB (REL-A), and P53.…”

Effects of USP7 on radiation sensitivity through p53 pathway in laryngeal squamous cell carcinoma

“…USP7 was reported to bind to the carboxy-terminus of p53, while p53 specifically recognizes the N-terminal tumor necrosis factor-receptor associated factor (TRAF)-like domain of USP7 [ 22 , 23 ]. p53, as the most frequently mutated genes in LSCC, plays a pivotal role in tumorigenesis, cell growth rates, and even tumor response to chemotherapy and radiation [24] , [25] , [26] . The mechanism of how p53 status affects the cellular response to radiotherapy involves signaling pathways in cell survival, growth, apoptosis, ferroptosis, and DNA repair [27] , [28] , [29] .…”

“…It was also confirmed that cell lines from head and neck cancer harboring disruptive p53 mutations were more radioresistant than those with p53-wild type or non-disruptive p53 mutations [31] . However, many studies reported that mutant p53 had no effect or even enhanced cellular sensitivity to radiation [32] . It is quite important to be aware that p53 could present different types of mutations, and other p53 mutations do not have the same biological effects, which need to be explored furtherly.…”

Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation

“…In contrast, high-LET radiation induced apoptosis without significant increase in p53 or p21/waf1 in these cells [ 167 ]. Mutations in p53 are associated with resistance to radiation-induced cell death and resistance to cell cycle regulation, especially mutations that affect p53 regulation of p21/waf1 [ 168 ]. Niemantsverdriet et al compared p53 phosphorylation at S37 (apoptotic signaling) and S315 (fibrotic signaling) by high- and low-LET radiation, and downstream regulation of the pro-fibrotic gene plasminogen activator inhibitor 1 (PAI-1) in transformed lung epithelial cells (A549) and immortalized, non-transformed human embryonic kidney cells (HEK) [ 169 ].…”