# Low Dose Ionising Radiation-Induced Hormesis: Therapeutic Implications to Human Health
###### Abstract  
The concept of radiation-induced hormesis, whereby a low dose is beneficial and a high dose is detrimental, has been gaining attention in the fields of molecular biology, environmental toxicology and radiation biology. There is a growing body of literature that recognises the importance of hormetic dose response not only in the radiation field, but also with molecular agents. However, there is continuing debate on the magnitude and mechanism of radiation hormetic dose response, which could make further contributions, as a research tool, to science and perhaps eventually to public health due to potential therapeutic benefits for society. The biological phenomena of low dose ionising radiation (LDIR) includes bystander effects, adaptive response, hypersensitivity, radioresistance and genomic instability. In this review, the beneficial and the detrimental effects of LDIR-induced hormesis are explored, together with an overview of its underlying cellular and molecular mechanisms that may potentially provide an insight to the therapeutic implications to human health in the future. radiation-induced hormesis; bystander effects; adaptive response; hypersensitivity; radioresistance; genomic instability +
Footnote †: journal: Medical Physics and Biomedical Engineering, University College London, Malet Place Engineering Building, London WC1E 6 BT, UK; [EMAIL_ADDRESS]  
Footnote †: journal: Medical Physics and Biomedical Engineering, University College London, Malet Place Place Engineering Building, London WC1E 6 BT, UK; andrew.nisbet@ucl. Assembly with Scientific Annexes; and Multidisciplinary European Low Dose Initiative (MELODI), a European radiation protection research platform, have defined low doses as those between 10 and \(<\)100 mGy and moderate doses from 100 mGy to 1 Gy and \(>\)1 Gy as high doses [8; 9; 10]. However, radiation protection and radiotherapy treatment strategies differ. Radiotherapy is given with either curative or palliative intent. Curative treatment usually involves the use of much higher doses (deterministic) than those considered in radiation protection with the expectation of prolonged survival to beyond five years in treated patients. From a radiation therapy view, low doses are \(<\)0.5 Gy, medium doses are 0.5-5 Gy, high doses are 5-15 Gy, and very high doses are \(>\)15 Gy [11]. Ionising radiation (IR), via signals from irradiated cells, can elicit detrimental biological effects such as altering cell functionality, induce mutations in cells to become malignant, or directly induce cell death resulting from DNA damage [12; 13; 14]. One significant characteristic property of ionising radiations is that the energy released with ionisation may break up the molecular structure of the substance upon which it falls, thus liberating ions or electrons and other different types of radiation that could induce a succession of cellular damage. Hence, ionising radiation can cause direct or indirect forms of DNA damage. Indirect damage occurs through the generation of reactive oxygen species (ROS) and free radicals through water radiolysis that may damage nucleic acids, oxidise proteins and lipids [12; 15; 16]. Ionising radiation can also directly affect deoxyribonucle acid (DNA) structure in the cells by inducing double-stranded breaks (DSBs) that pose a serious threat to genomic stability [16; 17]. Radiation-induced DNA lesions can ultimately lead to cell death (such as apoptosis, necrosis, senescence), mitotic failure and mutations if these DNA lesions are not correctly repaired or unrepaired [18; 19], the proportion of which depends on the absorbed dose [19; 20]. Relative to lower doses of IR, DNA damage is more severe with greater potential for adverse biological effects at higher doses and higher dose rates, as the DNA repair mechanisms become less effective. Similarly, it has been shown that increasing the linear energy transfer (LET) of the particle increases the lethality of the irradiated cells due to the inability of damaged cells to repair clustered DNA damage [21].