Radiation is energy travelling through Ionising radiation space – radioactive damage of the cells – tissues - organism

"Life on earth has developed with an ever present background of radiation. It is not something new, invented by the wit of man: radiation has always been there!"

Eric J Hall, Professor of Radiology, College of Physicians and Surgeons, Columbia University, New York, in his book "Radiation and Life"

What is ionizing radiation ? Penetration of ionizing radiation

ƒ Either particle radiation or electromagnetic radiation in which an individual particle/photon carries enough energy to ionize an atom or molecule by completely removing an electron from its orbit ƒ Ionising radiation produces electrically-charged particles ƒ Measures of ionizing radiation (units): called ions in the materials it – the amount of ionising radiation, or 'dose', received by a person is strikes (= ionisation) measured as energy absorbed in the body tissue, and is expressed in gray (Gy) – in the large chemical molecules of ƒ 1 Gy = 1 joule deposited per kilogram of mass (1 J/kg, formerly 100 rad) which all living things are made – equal exposure to different types of radiation expressed as gray do not the changes caused may be produce equal biological effects (1Gy of α-radiation will have a greater biologically important effect than 1Gy of β-radiation) → radiation effect is expressed as effective ƒ Types: dose, in a unit called the sievert (Sv). ƒ regardless of the type of radiation, 1 Sv of radiation produces the same biological – α = α–particles (Helium atoms) effect – β = electrons or positrons ƒ example: 1Gy=1Sv for γ-or β-radiation, 1Gy=10Sv for neutrons and 1Gy=20Sv – γ = electromagnetic (photons) for α-radiation – for radioactive substances rate of radioactive decay is expressed in –neutron becquerel (Bq) ƒ 1 Bq is one atomic decay per second)

Unstable atoms Radioactive decay

ƒ Atoms in a radioactive substance decay in a random fashion but at a characteristic rate ƒ Most atoms are stable: carbon-12 or oxygen- – the length of time this takes, the number of steps required and the kinds of radiation released at each 16 atoms remains the same forever step are well known –the half-life is the time taken for half of the atoms ƒ Certain atoms eventually disintegrate into a of a radioactive substance to decay (range from less than a millionth of a second to millions of years totally new atoms depending on the element) ƒ after one half-life the level of radioactivity of a – they are said to be “unstable” or “radioactive” substance is halved, after two half-lives it is reduced to one quarter, after three half-lives to one-eighth and so ƒ an unstable atom has excess internal energy, with the on result that the nucleus can undergo a spontaneous ƒ All uranium atoms are mildly radioactive change towards a more stable form = “radioactive – figure for uranium-238 shows the series of different decay” radioisotopes it becomes as it decays, the type of radiation given off at each step and the 'half-life' of – when an atom of a radioisotope decays, it gives each step on the way to stable, non-radioactive lead- 206 off some of its excess energy as radiation in ƒ Much of the natural radioactivity in rocks and soil the form of γ-rays or fast-moving sub-atomic comes from this decay chain particles ƒ unit: becquerel (1 Bq is one atomic decay per second)

1 Sources of ionizing radiation

ƒ Natural radiation ƒ Man-made radiation –cosmic – medicine ƒ positively charged ions from protons to Fe- ƒ diagnostic, therapeutic, sterilisation nuclei – commercial ƒ energy of this radiation can far exceed smoke detectors (americium-241) energies that humans can create even in the ƒ largest particle accelerators – industrial ( the dose rate from cosmic radiation on ƒ nuclear power plants (nuclear fission or airplanes is so high that, according to the nuclear fusion) United Nations UNSCEAR 2000 Report airline workers receive more dose on ƒ scientific – particle accelerators average than any other worker, including ƒ food preservation nuclear power plant workers ƒ agriculture (fertilising, increasing genetic –solar variability) ƒ all extremely hot objects (sun produces ƒ insect control ultraviolet and γ-radiation) ƒ water resources ( most solar radiation is electromagnetic ƒ analysing pollutants radiation, although the sun also produces particle radiation (mostly protons with ƒ industrial tracers relatively low in energy (10-100 keV) – non-radon terrestrial sources ƒ radiactive decay of natural isotopes (γ-ray emitters) in the rocks and soil – mainly potassium, uranium and thorium –Radon ƒ Radon-222 is produced by the decay of Radium-226 which is present wherever uranium is ƒ Radon is a gas, it seeps out of uranium- containing soils found across most of the world and may concentrate in well-sealed homes ƒ the single largest contributor to an individual's background radiation dose and is certainly the most variable from location to location ƒ Radon gas is the second largest cause of lung cancer in America, after smoking

Background radiation Uses of ionizing radiation ƒ Naturally and inevitably present in our environment ƒ diagnostic ƒ Levels can vary greatly – X-ray, computer tomography (CT), positron emission – people living in granite areas or on mineralised sands receive more tomography (PET) terrestrial radiation than others, while people living or working at – RIA (radioimmunoassay) high altitudes receive more cosmic radiation – scintigraphy - technetium-99m (skeleton, heart, circulation) ƒ A lot of our natural exposure is due to radon (gas seeps from the earth's crust and is present in the air we breathe) ƒ therapeutic – whole body/localised irradiation ƒ external sources - γ-rays from a cobalt-60 source ƒ internal sources - using a small dose of γ-or β-radiation (pleural cavity, intravaginal, …) – selective destruction by radioisotopes ƒ thyroid cancer – iodine-131 ƒ head and breast cancer – irridium-192 ƒ bone metastases – samarium-153 ƒ sterilisation – medical hardware, food

Protection from radiation, Radiation injury standards, regulation ƒ Types – external irradiation ƒ Limiting time: ƒ Radiation protection standards are based – for people who are exposed to radiation in on the conservative assumption that the – external contamination with radioactive materials followed by or addition to natural background radiation risk is directly proportional to the dose, transdermal absorption through their work, the dose is reduced and even at the lowest levels, though there is the risk of illness essentially eliminated by no evidence of risk at low levels – internal contamination by inhalation or ingestion with incorporation limiting exposure time – this assumption, called the 'linear no- of radiologic materials into the body's cells and tissues ƒ Distance: threshold (LNT) hypothesis', is – the intensity of radiation decreases with recommended for radiation protection ƒ These 3 types of exposure can occur in combination and can be distance from its source purposes associated with thermal burns and traumatic injuries ƒ Shielding: – it cannot properly be used for predicting – barriers of lead, concrete or water give the consequences of an actual exposure to good protection from penetrating radiation low levels of radiation ƒ for example, it suggests that, if the dose is such as gamma rays halved from a high level where effects have ƒ Example: nuclear detonation – radioactive materials are therefore often been observed, there will be half the effect, stored or handled under water, or by and so on. This could be very misleading if – heat (~35% of total energy) remote control in rooms constructed of applied to a large group of people exposed to trivial levels of radiation and could lead to ƒ heat and light cause thermal injury, including flash burns, flame burns, thick concrete or lined with lead inappropriate actions to avert the doses flash blindness (due to temporary depletion of photopigment from ƒ Containment: – practically, "As Low As Reasonably retinal receptors), and retinal burns – radioactive materials are confined and kept Achievable" (ALARA)” out of the environment - radioactive ƒ Much of the evidence which has led to – blast (~50% of total energy) isotopes for medical use, for example, are today's knowledge and standards derives ƒ blast wave results in fractures, lacerations, rupture of viscera, and dispensed in closed handling facilities from the atomic bomb survivors in 1945, – nuclear reactors operate within closed pulmonary hemorrhage and edema systems with multiple barriers which keep uranium miners, industrial catastrophes the radioactive materials contained - rooms (e.g. Chernobyl) animal experiments etc. – radiation (~15% of total energy) have a reduced air pressure so that any who were exposed to high doses incurred radiation causes the acute radiation syndrome (radiation sickness) leaks occur into the room and not out from in a very short time ƒ the room

2 Biological effect of ionizing Fatal × non-fatal DNA lesions radiation ƒ point mutations ƒ Direct ionization of macromolecules – ionized macromolecules almost never ƒ single strand breaks function properly, due to the fact that their function is largely controlled by their shape (SSB) and therefore by their charge distribution – breakage of disulfide bonds produces – reparation radicals ƒ Indirectly through the ionization (“radiolysis”) of water (~60% of body!!) ƒ double strand breaks – ionization of water produces "free radicals" - hydrogen and hydroxyl radicals - which are (DSB) very reactive, leading very quickly to the breakage of bonds in a biological molecule – lethal (apoptosis) (again, the macromolecule is rendered ineffective) – homologous recombination ƒ Three outcomes – cellular/molecular level: – cell cycle block → cell death – non-homologous end- ƒ interphasis (lymphocytes) ƒ mitosis or post-mitotic (other proliferating joining cells) – cell/DNA mutation (gene or chromosome) ƒ translocation ƒ reparation resulting in no residual damage ƒ cells incorrectly repair themselves resulting in ƒ insertion a biophysical change

DNA repair Character of biological effects

ƒ (in situ repair) ƒ Deterministic ƒ Stochastic – severity dependent – probability increases with ƒ excision repair (“determined”) on the dose the dose (not the severity!) –manifestation specific –manifestation non-specific – inter-individual – effect only when exposure – gradual increase of the risk variability in its exceeded threshold without “safe” threshold capacity – individual – damage of large amount of – damage of the single cell cells enough to cause effect radiosensitivity/ – onset rather close to the – manifestation delayed susceptibility to exposure (short latency) (typically years) damage –types: –types: ƒ acute radiation syndrome ƒ somatic mutation - cancer ƒ chronic post-radiation ( leukemias, thyroid, lung, syndrome breast, bones ( cataract, radiation ƒ germinative mutation dermatitis, (oocyte, sperm cell) – ƒ damage of the foetus in inherited genetic disease utero ƒ sterility

Overview effect types Acute radiation syndrome

ƒ Clinical components of the acute radiation syndrome include the hematopoietic, gastrointestinal, and cerebrovascular syndromes ƒ The time course and severity of symptoms for the component syndromes are different at different dose ranges – i.e. deterministic effect!!! – from few hours after exposure until few months following a radiation exposure

3 Acute radiation syndrome The hematopoietic syndrome ƒ Irradiation (>1Gy) of bone marrow ƒ Haematopoietic syndrome stem and progenitor cells at – lymphopenia, granulocytopenia (immunodeficiency), thrombocytopenia increasing doses results in exponential (bleeding), anemia cellular death - hematologic crisis ƒ GIT syndrome – hypoplasia or aplasia of the bone marrow + peripheral pancytopenia – early (hrs) - nausea, vomiting, diarrhea (predisposition to infection, bleeding, – later (days) - loss of intestinal integrity and poor wound healing, all of which ƒ malabsorption, dehydration, toxemia/sepsis, ileus, bleeding) contribute to death) ƒ Cerebrovascular syndrome ƒ While most bone marrow progenitors are susceptible to cell death after – headache, impaired cognition, disorientation, ataxia, seizures, prostration, sufficiently intense radiation doses, and hypotension subpopulations of stem cells or ƒ Cutaneous syndrome accessory cells are selectively more – erythema, burns, edema, impaired wound healing radioresistant, (presumably because – epilation (damage to hair-root cells Æ hair loss) of their largely non-cycling (Go) state) – play an important role in recovery of hematopoiesis after exposure to doses as high as 6 Gy, albeit with a reduced capacity for self-renewal ƒ Anemia is delayed due to long life- span of erythrocytes (~120 days)! ƒ Massive stress reaction (glucocorticoids release) partly contributes to lymphopenia (due to their cytolytic action) and paradoxically delayed granulocytopenia (due to release of additional granulocytes from spleen)

Embryo, foetus, germinative Psychological impact of cells - summary radiation exposure ƒ Pregnancy - damage of the foetus in utero Approx. 75% of individuals exposed to nuclear – <3 weeks (blastogenesis) ƒ ƒ “all or nothing” weapon detonations or industrial accidents (victims ( gene and chromosomal mutation usually lead to abort as well as participants in radiation cleanup) exhibit –3 –8th week (organogenesis) some form of psychological symptoms ƒ growth retardation ƒ teratogenic - congenital deformalities – inability to sleep, difficulty concentrating, social withdrawal ( microceohlay, microphtalmia, spina bifida, cleft palate, … –8 –15th week (eraly foetal period) ƒ In addition, exposed individuals and their families ƒ mental retardation have a high rate of post-traumatic stress disorder ƒ cancer susceptibility in born children (leukemias) – symptoms include anxiety disorders, depression, a recurrent –later sense of re-experiencing the traumatic event, outbursts of ƒ rather resistant anger, an exaggerated startle response, and increased ƒ Sterility irritability ƒ spermatogenesis - temporary sterility in males ƒ post-traumatic stress disorder can be diagnosed when these ƒ ovaries - much higher doses required to induce sterility in females symptoms persist for more than 1 month ƒ Germinative mutations – inborn abnormalities

Medical management of ARS

ƒ blood transfusions ƒ cytokine therapy – granulocyte macrophage colony-stimulating factor (GM-CSF) – granulocyte colony-stimulating factor (G-CSF) ƒ bone marrow and stem-cell transplantation ƒ antibiotics and chemoterapeutics ƒ prevention of thyroid cancer – potassium iodide (reduction of radioiodine uptake when present) by saturating the thyroid gland with non-radioactive iodine

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