Section snippets
Ionising radiation exposure
DNA damage is a constant threat to genomic integrity and may arise endogenously or be induced exogenously by environmental mutagens such as ionising radiation ( IR ) [ 1 ]. Perhaps the most toxic type of IR-induced DNA lesion is the DNA double-strand break ( DSB ), formed when both strands of the phosphodiester DNA backbone are broken . Potentially lethal to cells at even a singular occurrence , DSBs are generally detected and repaired with great speed , with Non-Homologous End-Joining ( NHEJ ) serving as
Radiation linear energy transfer , DNA damage complexity and repair
A definition commonly used to describe the impact of different qualities of IR is relative biological effectiveness ( RBE ), the dose ratio of low-LET to high-LET IR needed to produce the same biological effect . For high-LET neutrons , the RBE is 2 – 4 relative to low-LET X-rays ; in other words , the high-LET IR is 2 – 4 times more effective at killing cells than an identical dose of low-LET IR [ 5 ]. In terms of human health , high-LET IR is classified by many authorities , including the United Nations
Implications of the low-dose , chronic modality of high-LET IR exposure
In the vast majority of human cases , high-LET IR-induced DSBs are induced at low dosage but chronically , over the course of years or decades . The best example of this is alpha particle irradiation due to radon gas inhalation , which accounts for 40 – 50 % lifetime IR exposure for much of humanity [ 48 ], [ 49 ]. In that situation , inhaled gaseous 222 Radon will , after emitting an alpha particle , decay into solid 218 Polonium that precipitates within lung tissue and emits alpha radiation for several
A brief synopsis of NHEJ and its role in high-LET IR-induced DSB repair
To ensure genomic stability , organisms have evolved two predominant DSB repair pathways : NHEJ and homologous recombination ( HR ). NHEJ requires no undamaged DNA template and functions throughout the cell cycle , being exclusively favoured in G0 , G1 and early S-phase ( where no homologous copy of each chromosome is present ) and the preferred pathway for two-ended DSBs under most conditions [ 39 ], [ 67 ]. HR operates chiefly on DSBs resulting from collapsed DNA replication forks or highly resected DSBs
Exposure to α-particles via radon gas inhalation
By far the most prominent source of IR exposure for humanity is radon gas derived α-particles ( helium nuclei ), accounting for approximately half of the world population ' s annual exposure [ 4 ], [ 49 ]. Radioactive 222 Radon arises naturally from the decay of solid , earth-bound 226 Radium , itself part of the decay series of 238 Uranium . As the first ( and only ) gaseous element within that decay series , radon gas will diffuse upwards from the high pressure environment of soil gases , through foundational
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