# Low Dose Ionising Radiation-Induced Hormesis: Therapeutic Implications to Human Health
###### Abstract
However, the beneficial effects of a low irradiation dose (\(\leq\)100 mGy) currently remain unclear and controversial despite reports that several cellular protective mechanisms are stimulated [22]. Annually, it has been estimated that human beings and other living organisms are typically exposed to radiation doses of some few mSv from natural background sources, extra-terrestrial as well as in soil and water [23; 24]. Ionising radiations are forms of electromagnetic waves (\(\gamma\), X-rays) or particles (neutrons, protons, \(\beta\) or \(\alpha\)) that are typically used in medical interventions such as diagnostic radiology, nuclear medicine and radiation therapy [23], with other situations of utilisation and exposure arising in industry. With these increasing involvements of radiations, the low-dose ionising radiation (LDIR) effects on humans are of great concern to public health. The main question has been what is the lowest dose threshold that a human could be exposed to without detrimental effects being suffered, both post exposure and for future generations. Previously, the ICRP (1990) and the NCRP (1993) have recommended that the estimates of cancer risk for low-dose exposure be extrapolated from higher doses where the data are principally from the cancer incidence found in survivors of the atomic bombs in Japan [25; 26]. There has been a long-standing controversy on determining the lowest dose threshold that could be considered safe for humans. The focus has been on how best to extrapolate cancer risks from high doses to low doses, and since there is much uncertainty concerning the lower dose points, epidemiologic data do not extend to the low doses for radiation protection. [PERSON] and [PERSON] (2019) [27] have succinctly described the controversy of the four different types of curves, as shown in Figure 1a-d. Figure 1a assumes that risks are greater at low doses than would be predicted from a linear extrapolation (low-dose hypersensitivity, a quasi-threshold dose) before repair kicks in. Figure 1b demonstrates the linear-no-threshold (LNT) hypothesis that has been much disputed due to the discovery of non-targeted effects that demonstrate a non-linear response at low dose. Figure 1c assumes that there is a threshold in dose, below which there are no deleterious biologic effects, known as deterministic effects. Finally, Figure 1d shows the hormesis affect with a threshold dose that when exceeded, will have detrimental effects [27]. Hormetic dose responses are biphasic and are generally represented by a non-linear relationship, either as an inverted U- or J-shaped dose-response curve, which is very much dependent on the endpoint measured [28]. Moreover, different types of radiation, tissue types, dose and dose rate also play important roles [29], albeit below the order of 100 mGy, to protect against genomic instability and cytogenetic damage [30,31]. Additionally, these inverted U- and J-shaped curves contain two thresholds. The inverted U-shaped curve displays the toxic traditional threshold or zero equivalent point, however, when the response crosses the control response, it becomes inhibitory. Conversely, the J-shaped curve (hormesis) demonstrates the lower dose threshold, whereby the stimulatory response decreases and in time reverts to being indistinguishable from the control and with increasing dose results in detrimental effects [28] as shown in Figure 1a,d. In the 19 th century, the biphasic dose-response phenomena were first observed in yeast experiments performed by [PERSON], in which a low dose of numerous disinfectants stimulated yeast metabolism. Later, the dose-response theory of [PERSON] and [PERSON] was established and became more conceptualised based on their observation that low dose of revartime was effective in the treatment of gastroenteritis by its biphasic characteristic. This induced the adaptive response of the host, resisting infection but not killing the bacterial itself, hence enhancing survival [32].