Health Effects of Exposure to Ionising Radiation

Purpose: The effects of ionising radiation on the human body has been discussed. The authors believe that the understanding of the radiation incidents from the perspective of its effects is crucial for better preparation, and therefore safer and more effective responses to incidents involving such threats. Introduction: The increasing use of radioactive materials and radiation producing devices in many areas of our lives carries the risk of exposure to high doses of radiation being hazardous to our health due to possible damage to radiation sources or improper handling. Exposure resulting from the inten tional use of radioactive materials for criminal or terrorist purposes cannot be excluded, either. Exposure to ionising radiation may cause adverse health effects both to victims of a radiation incident and for rescuers providing emergency care. Such threats require the proper preparation of emergency medical services (EMS). Part of these preparations is to examine the specifics of radiation hazards, including radiation sources, the mechanism of injury of ionising radiation and the type of radiation damage. Methodology: The publication presents the properties of ionising, corpuscular and electromagnetic types of radiation, which are the most important from EMS’s perspective. The dangers of contact with a radiation source, the problem of external and internal contamination, the estimation of the amount of absorbed radiation were discussed, and the interrelationships between them were presented. The mechanism of direct and indirect action of ionising radiation on cell structures (DNA, mRNA, cytoplasmic membranes) and intracellular enzymes was thoroughly discussed. The authors presented health consequences of radiation for the body in the form of acute (deterministic) lesions and late (stochastic) lesions. Conclusions: Particular attention was paid to acute radiation syndrome (ARS). The dependence of ARS on the amount of absorbed radiation was dis cussed in detail. Four stages of ARS were presented: initial, latent, manifest illness and recovery (or death) as well as the time of their onset, duration and end. The mechanism of damage to individual organs and systems was also analysed. The most common symptoms, their severity, and causes of life-threatening conditions, resulting from radiation damage in particular syndromes of ARS, were indicated. In addition to systemic effects, local changes in the form of Cutaneous Radiation Syndrome (CSR) were discussed.


Introduction
Ionising radiation has been present since the beginning of the Universe. The early Earth was penetrated by much higher radiation than that we are exposed to now. The composition of the Earth's crust with deposits of radioactive elements incl. uranium, thorium, radium has been a major source of natural radiation [1].
Part of natural radiation emanates from the ground, which is called background radiation and its values differ. The average annual dose in Poland is 2.43 mSv from natural sources [2]. In numerous European countries average natural background exposure is higher e.g. in Norway, Switzerland, Finland and Spain. In some parts of Norway and Sweden natural exposure ranges from 10 to 35 mSv per annum, but it is not the highest value in the world, as there are areas where even higher natural exposure has been observed. In Ramsar, a city in Iran, annual radiation exposure equals 132 mSv per year, whereas the maximum allowable annual dose of radiation for employees is 20 mSv [1], [3]. In general, the indoor radiation may be higher than the outdoor one. All living organisms consist in radioactive elements, and that is why every organism emits radiation. For instance, a human being is a source of radiation due to radioactive potassium present in his or her body. It makes up 0.012% of the total amount of potassium, which is the source of radiation of 0.17 mSv per year [4][5][6].
Another source of radiation is cosmic radiation, which is mostly SFT VOL. 55 ISSUE 1, 2020, PP. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] absorbed by the Earth's atmosphere and only its small fraction reaches the Earth's surface. The level of cosmic radiation dose in Poland is merely 11.8% of the total annual dose [7]. is an increasing man-made radiation source [8]. A single chest CT scan delivers 3 mSv, which is equivalent to the radiation dose of 150 chest X-rays while a head CT scan equals 4 mSv, which corresponds to 200 chest X-rays [9]. According to radiation regulations and laws, an average person may receive an effective dose of 1 mSv per a single calendar year. An effective dose may be greater than 1 mSv unless a total dose of 5 mSv in 5 consecutive years is not exceeded [10]. The authors are inclined to believe that due to a common use of radioactive materials and related risks it carries, the understanding of ionising radiation effects on a human body should be paramount for EMS workers. The aim of this paper is to present the impact of ionising radiation on a human body and health effects of highdose radiation.

Ionising radiation
A human being is constantly exposed to different sources of radiation incl. ionising radiation. Ionising radiation is a form of energy emitted in the form of particles or electromagnetic waves that may result in the production of harmful and potentially lethal ions.
There are several types of ionising radiation, each with different properties such as its range, penetrating power and ionising power.
Ionising radiation protection is presented in Figure 1.
Możliwości osłony przed promieniowaniem jonizującym przedstawiono na rycinie 1. The source of radiation may be any material including radioactive isotopes or ionising radiation-producing devices e.g. X-ray machines, CT scanners. Radioactive sources are divided into a sealed source, in which the radioactive material is prevented from escaping or being released and an unsealed (closed) source, which refers to any radioactive material which is not encapsulated or contained [13]. Radioactive liquids or solids that come in direct contact with people cause external contamination. Internal contamination occurs when radioactive material is inhaled, ingested or incorporated via wounds. Radiation producing devices (e.g. X-ray machines, CT scanners) do not cause contamination.

Radiation doses
Since radiation is the energy deposited in matter, the knowledge of the absorbed doses by tissue is crucial to assess the risk of radiation effects. Radiation absorbed dose which is defined as one Joule of energy absorbed per kilogram of matter. The SI unit of measure is the gray (Gy). Owing to the fact that different ionising abilities refer to a specific type of radiation, an equivalent dose has been introduced. An equivalent dose is based on the absorbed dose to individual tissues or organs taking into account the type of radiation, and thereby the amount of energii and its force. An equivalent dose allows for precise assessment of biological damage of a certain type of radiation to exposed tissues.
The SI unit of measure is the sievert (Sv). An effective dose is calculated by multiplying an absorbed dose (Gy) by a radiation weighting factor to a specified radiation type. The values radiation weighting factor are presented in Table 1. Gray and sievert are the units expressing high amounts of absorbed energy.

5-20
Beta / Beta 1 Gamma and X-ray / Gamma i rentgenowskie 1 Most of ionising radiation detection devices (e.g. Geiger Mueller (GM) Detectors) do not measure an absorbed dose but only an exposure dose, which is the amount of single ion pairs produced in a gas-filled chamber. The exposure dose is based on the amount of the total charge of the ions in air produced by photons of ionising radiation. The SI unit of exposure to radiation is C/kg (coulomb/kilogram) and is the total electrical charges produced in a volume of air of mass. The unit for exposure has no name and is expressed as C/kg and a previously used roentgen unit was related to 1R = 2.58 × 10 -14 C/kg. The exposure dose expresses exposure per hour (mSv/h). In order to assess biological effects of radiation on the human body it is crucial to measure an absorbed dose or even an equivalent dose.

Biological effects of irradiation
Ionising radiation-induced damages lead to local and systemic radiation lesions and injuries. Damage to biological material is the result of the energy deposited in particles of cellular structures. There are three phases of radiation influence on cells: physical, chemical and biological. In the physical phase, the radiation pushes an electron in the DNA molecule (strand of deoxyribonucleic acid) out of its orbit, which disrupts its structure. In the chemical phase, high energy induces ionisation (radiolysis) of water molecules (OH−, H+), which leads to the production of free radicals (•OH, HO 2 •) and chemical bonds are either broken or new ones are formed [14]. Free radicals damage cellular structures and thus cells in the biological phase. DNA, mRNA, enzymes (catalase, peroxidase) and cytoplasmic membranes are mainly damaged [15]. Some of those damages that are beyond repair lead to cell death or its lysis (decomposition and elimination). In other cases changes to DNA survive and may be passed to a subsequent cell generation.
Apart from the damage resulting from water radiolysis, there is an indirect damage resulting from the Compton Effect (Compton Scatter) and the photoelectric effect [16]. Two models of DNA chain damage are presented in Figure  SFT VOL. 55 ISSUE 1, 2020, PP. 32-47 Prenatal ionising radiation exposure may be teratogenic (disturbing the embryo development), carcinogenic, or mutagenic.
Health effects from radiation exposure depend on the radiation dose and the stage of embryonic development. An embryo is particularly sensitive to radiation during the period of organogenesis (two to seven weeks after conception) and in the early fetal period (eight to 15 weeks after conception) [18]. The effects of exposure to radiation may be classified as deterministic and stochastic ones.

Deterministic effects
Deterministic effects of ionising radiation result from exposure to radiation with a threshold dose exceeding 1Gy delivered in a short period of time (a single dose). Irradiation above a threshold dose causes temporary or permanent damage to tissues and thus damage to the organs and systems. Deterministic effects most often occur from 2 to 4 weeks after the radiation exposure and are manifested as bone marrow (hematopoietic), gastrointestinal, cardiovascular [19]. Local reactions and skin lesions may occur alone or with general symptoms due to ionising radiation. Although many organs are in fact damaged, the signs and symptoms are varied, depending on the dose and on extent of the damage to the organs and systems.     SFT VOL. 55 ISSUE 1, 2020, PP. 32-47 The human body's reaction to radiation depends upon several factors. The most important factors are as follows: an absorbed dose, a radiation type (alpha, beta, gamma, neutron radiation), radiation exposure, a kind and size of exposed tissue, age, health condition and what is crucial the quality of medical care provided incl. possibilities and skills of EMS to respond within first minutes and hours after radiation exposure [19].
Radiosensitivity of specific organs and tissues differ. Minor biological effects are noticed in sensitive organs such as testicles when exposed to radiation greater than 0.15 Sv causing temporary infertility or bone marrow affected by a dose of 0.5 Sv (impaired/weakened hematopoietic function) [20]. The above changes are in most cases temporary and leave no permanent effects. It appears that cells characterised by high proliferative activity and low maturity are particularly susceptible to radiation [21]. The most radiosensitive cells are the gonads, bone marrow and intestinal epithelium, while the least sensitive are nerve and muscle cells [22]. The term Acute Radiation Syndrome (ARS) is used to describe signs and symptoms of damage induced to organs and system that may lead to death within days or many months. ARS is also termed acute radiation sickness occurs when the whole body or its significant part receives radiation above a threshold dose of 1 Gy of gamma radiation (or mainly a drop in lymphocyte count was observed [23]. Signs and symptoms of ARS are expected to occur after being exposed to a threshold dose of 1 Gy. One of the most important indicator is the lethal dose within 60 days (LD50/60). It is the dose of radiation that leads to death to 50 percent of an exposed population in 60 days. The LD 50/60 is in the range from 3.5-4.0 Gy in patients managed without specialised care provided, 4.5-7 Gy when antibiotics and appropriate advanced treatment are provided and up to 7-9 Gy in patients with immediate access to intensive care units, reverse isolation and hematopoietic cell transplantation.
It is paramount for the medical management of a radiation incident to determine whether a person has absorbed a threshold dose of ionising radiation above 1 Gy (or its equivalent 1 Sv).
A threshold dose of 1-6 Sv leads to the damage to hematopoietic system which is particularly radiosensitive and is followed by hematopoietic syndrome. Other organs are less affected.

Prodromal phase
The prodromal phase begins usually within first 48 hours, but may develop up to 6 days after exposure [24]. Signs and symptoms are characterised by depression, anxiety, nausea, vomiting, dizziness, headache and sleep disturbances. Symptoms may occur from minutes following high-dose exposure to ionising radiation or an hour or a few hours after exposure if doses were less. Depending on the dose, a prodromal phase is followed by either a latent phase (low doses) or a manifest illness phase (high doses). The assessment of the time course of signs and symptoms (especially nausea and vomiting) and their severity may indicate the approximate absorbed dose [25]. This radiation triage was primarily intended to be used in the aftermath of a nuclear war which would involve mass casualties. Today, the radiation incidents involve few casualties and thus the radiation triage is of lesser importance due to more accurate solutions to be employed such as lab blood tests (the dynamics of lymphocyte count changes, chromosome aberration analysis).
More detailed analysis of radiation triage and laboratory diagnostic methods will be presented in the following subsequent paper where the medical management of radiation incidents is thoroughly discussed. Table 3 presents characteristics of the prodromal phase of acute radiation syndrome (ARS).

Manifest illness phase
The third stage of ARS is characterised by the full manifestation of organ or system dysfunctions. If a person survives this phase, recovery is likely [20]. The critical phase of the hematopoietic syndrome occurs within 3-4 weeks after the bone marrow injury that causes the inability to produce sufficient amount of blood cells that consequently leads to immunodeficiency. Damage to intestinal epithelium occuring after a few days impair water-electrolyte balance followed by cardiopulmonary failure [26]. In the car-

Recovery or death
The last stage is recovery or death. It is difficult to predict whether the total radiation absorbed dose of ionising radiation is lethal for a particular patient. There are a few cases of patients who survived apparently lethal doses of radiation (Goiânia, Brazil). They involved radiation which was fractionated into smaller doses within a prolonged period of time. Additionally it penetrated body parts assumed to be "safe" from the biological effects' perspective [27]. Age and sex are important factors that are to be taken into consideration while assessing radiation risks.
Men tend to be more susceptible (higher radiosensitivity of their immune system) to adverse effects of radiation than women.

Cutaneous radiation syndrome
The cutaneous symptoms that occur after radiation exposure are caused by a combination of inflammatory processes and proliferation changes [32]. Cutaneous radiation syndrome (CRS) may be a prompt reaction to radiation exposure. The radiation damages connective tissues and the blood vessels of the dermis. Transient erythema has been observed a few hours after the radiation exposure to 2 Gy [30]. The process may take years. soft tissues and even muscles and bones [30]. Long-term effects include keratosis, hyperpigmentation, hypopigmentation, epidermal atrophy, fibrosis, ulceration, telangiectasias and extravasation [34][35]. The extent and dynamics of cutaneous responses depend on several factors such as a dose, type and intensity of radiation, individual radiosensitivity, the extent of radiation exposure, contamination and absorption and the volume of skin exposed. It has been proved that repeated exposure to radiation results in cumulative doses and increases the radiation-induced damage to the skin. The skin covering bony areas show higher sensitivity to radiation [36]. Basal-cell and squamous cell skin cancers may occur years after exposure [37]. Extensive damage to the skin alter LD50/60 and increase the risk of death after every radiation exposure irrespective of the absorbed dose [38].

Stochastic effects
Stochastic effects are assumed to be dose-independent. It is believed that a dose rate may only cause the increase in the probability of disease occurrence. Stochastic effects have no threshold level, which means the effects may occur after low-dose radiation exposure [39]. Stochastic effects include leukemia, solid tumors and hereditary defects passed on to children [40]. Neoplastic transformations may occur many years after the expo-

Conclusion
Various sources of radiation have always been present around us. Nuclear energy, medical devices producing radiation or containing radioactive material, diagnostic and measuring devices used in industry and radioactive waste repositories are the main sources of potential hazard sources. The amount of artificial radiation a man is exposed to increases every year.
The risk of radiation incidents resulting from failures of radiation producing devices (diagnostics, radiotherapy), human error or intended use of radioactive materials for criminal purposes must be considered. We cannot exclude that incidents such as the Chernobyl or Fukushima disasters will reoccur in the near future. The use of radioactive materials has been the target of terrorists. The state security services are aware of the real risk of a "dirty bomb" being constructed and detonated. The authors of this paper intended to discuss the medical approach of radiation incidents and their effects. The authors believe that the post-cold war peace is deceptive and makes emergency services less alert towards the ionising radiation risks.