Physical Agents - Radiation PDF

INJURY CAUSED BY PHYSICAL AGENTS RADIATION  RADIATION IS ENERGY THAT TRAVELS AT HIGH SPEED IN THE FORM OF WAVES OR PARTICLES Electromagnetic radiation: energy is measured in Electron volts (eV) Corpusculate radiation: since they have a mass, ener...

INJURY CAUSED BY PHYSICAL AGENTS RADIATION  RADIATION IS ENERGY THAT TRAVELS AT HIGH SPEED IN THE FORM OF WAVES OR PARTICLES Electromagnetic radiation: energy is measured in Electron volts (eV) Corpusculate radiation: since they have a mass, energy corresponds to KINETIC ENERGY: E= ½ mv2 Effects of ionizing and non-ionizing electromagnetic radiation Energy of the radiation is described by E=hv ; h= Planck constant; v (ni)=frequency as frequency / wavelength () are inversely proportional, then the relationship becomes E=h/ Radiation that has high wavelength has a low energy Classification of electromagnetic radiation ENERGY  Radiation Effect energetic changes energy < 1 eV Thermal Oscillation and displacement of the atoms due to increase EFFECTS ON MATTER in the vibrational, rotational and translational motions. AS A FUNCTION OF ENERGY Passage of an electron from < 10 eV Exciting one orbit to another, which is outermost and less bound to the nucleus. The bond between an electron > 10 eV Ionizing and the nucleus of the atom is broken, generating a pair of ions, one negative, the free electron, and one positive, the atom without an electron  EXCITING RADIATION:UV RAYS UVC is the most dangerous type of UV radiation, but fortunately, the sun’s UVC is absorbed by our atmosphere before it reaches the earth’s surface. UVB is the second most potent type of UV radiation. It penetrates the top layer of the skin and is the main cause of basal cell and squamous cell carcinoma as well as melanoma. UVB is also responsible for making vitamin D. UVA is the least potent type of UV radiation but most abundant. 95% of the UV light that reaches us is UVA. It does not increase your vitamin D levels. UVA penetrates clouds and car windows. UVA radiation penetrates deep into the skin, and causes wrinkling, leathering, and premature aging of skin. It makes UVB-induced damage worse, and increases risk for developing melanoma and other skin cancers. IN THE ATMOSPHERE, RADIATION IS ABSORBED BY: ATMOSPHERIC OZONE WATER CARBON DIOXIDE OXYGEN NITROGEN AIR POLLUTANTS Window panes absorb UVB but transmit UVA  Due to the shallow depth of penetration of UV radiation into human tissues, the organs sensitive to its exposure are the skin and eyes. IMMEDIATE EFFECTS: LATE EFFECTS: single exposure or few prolonged these occur for exposures that are exposures constantly repeated over time for work 1) Inflammatory reaction of the skin or even aesthetic reasons = (erythema) and conjunctiva 1) premature aging of the skin (conjunctival inflammation) that (keratosis, thickening of the epidermis, resolves quickly without leaving relics roughness, etc. (UVA). (UVB). 2) cataracts (UVA). 2) Damage to Langherans cells and 3) skin cancers (squamous cell keratinocytes (UVB). carcinoma and basal cell carcinoma - 3) Melanogenesis is stimulated in basal cell carcinoma- and melanoma) melanocytes (UVB). (both UVA and UVB).  MECHANISMS OF UV DAMAGE Direct Photochemical Mechanism Direct interaction between radiation and biological material: matter absorbs  of energy that causes electrons to pass from one orbital to another, and an excited molecule is generated. On the skin, the excitable molecules are called CUTANEOUS CHROMOPHORES: Endogenous of the epidermis: purine and pyrimidine bases of nucleic acids, melanin, aromatic amino acids -Phe, Trp, Tyr-, numerous lipids. Endogenous of the Dermis: Hemoglobin, -carotene, bilirubin. Exogenous: tattoo ink. Between 200 and 300 nm is in the absorption spectrum of the most important biological molecules, so UVB and UVC act with a direct mechanism Formation of Thymine dimers When UV radiation hits a strand of DNA, it is possible that two consecutive thymines absorb its energy to form a covalent bond. This results in the formation of a thymine dimer, a serious DNA lesion that alters genetic information (it is the most common form of damage produced by UV). IONIZING RADIATION Ionizing radiations are capable of causing, directly or indirectly, the ionization of the atoms and molecules of the materials they pass through. As these radiations pass through matter, they are able to tear away, an electron from the outer orbit of an atom thus creating an ion pair. ENERGY > 10 eV IONIZING RADIATION CORPUSCLE RADIATION : Sub-atomic particles* moving at high speeds, often close to the speed of light ( e  particles). DIRECTLY or INDIRECTLY IONIZING (Neutrons only) ELECTROMAGNETIC RADIATION: Photons propagating at the speed of light (X e  rays). INDIRECTLY IONIZING * Elettroni o positroni (particelle - e + ), 2 protoni + 2 neutroni (particelle ), protoni, neutroni SOURCES OF EXPOSURE NATURAL: Cosmic rays, radioactive elements in rocks (uranium), Radon (Natural, odourless, tasteless and colourless radioactive gas, volatile and soluble in water. Ubiquitous, naturally present on earth). ARTIFICIAL: Sources used in diagnostics and therapy (Radiopharmaceuticals, Radiotherapy, Radiodiagnostics, Research) If a radiation is corpuscular, since with a mass, the likelyhood of being stopped by matter in the environment is high.  Radiation results from the natural decay of radioisotopes or the artificial acceleration of subatomic particles Radioisotopes are atoms with unstable nuclei The return to stability occurs by emission of particulate radiation (α e β particles) e/o nonparticulate (γ ed x radiation) This emission therefore represents radioactive decay or radioactivity and can be natural (e.g. uranium mines) or induced (e.g. particle accelerators) RADIATION DAMAGE result from: - DIRECT ACTION - INDIRECT ACTION  EFFECTS AT THE MOLECULAR LEVEL DIRECT EFFECTS INDIRECT EFFECTS (particulate) (X e γ radiation; neutrons) are carried out directly on sensitive molecules, depend on the radical species that are especially produced by the interaction between PROTEINS ionizing radiation and water NUCLEIC ACIDS WATER RADIOLYSIS H2 O H+ + OH  DIRECT EFFECTS The radiation directly affects the biological molecule TARGET → Larger molecules are more likely to be affected: DNA> RNA > proteins > sugars > lipids Direct damage: the larger a molecule is, the more likely it is to be affected. the probability that a molecule will be affected depends on its size, but also on how many molecules of a certain type there are: DNA and RNA are large but in terms of the number of molecules they are not the main components of a cell. This is why most biological damage from radiation is the consequence of the action on macromolecules of free radicals produced by the ionization of water (Indirect damage). The cells and tissues of living organisms consist mostly (60-80 %) of water and the remainder of various molecules and atoms. The most common atoms are H, O, C, N, P, S, Ca. PROTEINS: both the β-sheet and α-helix structures are maintained by H-bridges and disulfide bonds. Proteins subjected to the direct effects of ionizing radiation are subjected to readjustment of the electric charges and the oxidation of the sulfhydryl groups, and therefore lead to denaturation with loss of activity i.e. for enzymes. NUCLEIC ACID: the direct action of ionizing radiation on DNA can occur on a single strand or on both strands of the double helix. i.e.: removal of the two helices due to the breakage of the hydrogen bonds; loss of a base; modification of a base (deamination); single- or double-strand breakage; formation of thymine dimers; intra-DNA bonds.  INDIRECT EFFECTS they derive from the action of free radicals formed as a result of the direct action on water (radiolysis) and on oxygen They are the main cause of biological damage since water is the main component: it is the most likely affected (for each DNA molecule there are about 1.2 X 107 molecules of H2O) The formation of FREE RADICALS, especially the hydroxyl radical (OH°) in the context of tissues, is thought to be the most important cause of ionizing radiation injury. It would be far more important than the direct action of ionizing radiation. FREE RADICALS are very unstable RADICALE OSSIDRILE RADICALE IDROGENO HYDROXYL RADICALS are very powerful oxidant of various organic substances: OH° + S → OH- + S+ They can also react with each other to produce hydrogen peroxide: OH° + OH° → H2O2 HYDROGEN RADICALS react with molecular oxygen to form another highly reactive radical, the hydroperoxide radical: H° + O2 → HO°2 REACTIVE OXYGEN SPECIES OXYGEN present in tissues can also be affected by radiation (corpusculate, gamma, electrons) and generate a variety of reactive species Different tissues have a different chance of being damaged by ROS: - depending on their O2 (pO2) tension (it will be higher in the skin and lungs) - depending on the amount of anti-oxidants present.  ENDOGENOUS ANTIOXIDANTS enzymatic: SUPEROXIDE DISMUTASE (SOD), CATALASE, GSH PEROXIDASE. They act on radical or oxidizing molecules (H2O2) by converting them into harmless molecules. Antioxidants are not unlimited molecules, they can fail to neutralize OXIDATIVE STRESS EXOGGENOUS ANTIOXIDANTS: VIT A, VIT C, BETA-CAROTENE In general, the radiosensitivity of a tissue also depends on its anatomical location: Highly exposed tissues are more radiosensitive: e.g. the skin, the retina  Positron Emission Tomography Some common examples of radioisotopes used in PET imaging include: 1.Fluoro-18 (F-18): It is used in the form of fluorodeoxyglucose (FDG) for the detection of metabolic activity, often used in the diagnosis of tumors and in the evaluation of brain pathologies. 2.Carbon-11 (C-11): It is used in various compounds to study cerebral perfusion, central nervous system receptors, and other biological processes. 3.Oxygen-15 (O-15): It is used to study cerebral blood flow and brain function. 4.Nitrogen-13 (N-13): It is used to assess cardiac perfusion. These radioisotopes emit positrons during radioactive decay, and their detection allows the generate images (PET imaging) Used in nuclear medicine to diagnose and study various biological processes in living tissues.  PET imaging heart brain PET is capable of detecting biochemical processes as well as expression of some proteins. PET scanning does this by using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Regional tracer uptake in various anatomic structures can be visualized and relatively quantified in terms of injected positron emitter. LA RADIOTERAPIA Radiation therapy is based on the principle of directing ionizing radiation at cancer cells to damage their DNA. While healthy cells have mechanisms to repair damage to their DNA, cancer cells often have much less efficient mechanisms, so damage is more likely to be lethal to this type of cell. The main limitation in the use of this technique is that the cells of solid tumors are in oxygen debt (hypoxia) and this makes them more resistant to radiation the lower the presence of oxygen. Oxygen contributes to cytotoxicity to cancer cells through the production of free radicals. Techniques are being tested to increase oxygenation during radiotherapy treatment, or decrease oxygen in the healthy tissues surrounding tumors to limit biological damage. Radiotherapy can use both electromagnetic radiation (X-rays and g-rays) and particulate radiation. X-ray radiography If a complex structure (such as a man's chest, for air filled lung example) is interposed between the X-ray source and the film, the structures made up of atoms with rib a high atomic number (Ca and P) and a high thickness (bones), which almost completely retain radiation, appear clear on the film; those that only heart partially retain them (muscles, vessels, etc.), appear gray; those that are almost completely crossed (lungs) are dark. The combination of these components, light, grey and dark, makes up the radiographic image and the impressed film is called a radiogram or radiography. Ionizing radiation has different effects on organisms depending on: - Cell division rate of irradiated tissue (the greatest sensitivity is found in: bone marrow, skin, intestinal mucosa, germ cells) - H2O and pO2 content - Dose and duration of exposure - Route of exposure: external or internal radiation A distinction is made between: acute effects: occur as a result of the absorption of very high doses of radiation in a short period of time (e.g. accidents in nuclear power plants) chronic effects: they derive from continuous and prolonged exposure over time to small doses of radiation (daily occurrence of some professional activities) somatic effects: they affect the cells of the different tissues of the irradiated person's body genetic effects: they concern the cells of the reproductive system, through which they could be transmitted to offspring RADIATION DOSE The DOSE/EFFECT ratio is extremely varied, depending on many parameters: Nature of radiation: (corpusculated: alpha, beta; or electromagnetic G- rays and X-rays) Irradiation mode: (external or internal) Extent of irradiated body surface area  Per dare un'idea del valore di 1 Sv EVENTO DOSE ASSORBITA RADIOATTIVITA’ NATURALE 2,4 × 10-3 Sv per anno RADIOGRAFIA ORDINARIA 1 × 10-3 Sv TAC 3 ~ 4 × 10-3 Sv PET o SCINTIGRAFIA 10 - 20 × 10-3 Sv RADIOTERAPIA decine di Sv, anche oltre i 40 Sv, concentrate sul tumore  DOSE EQUIVALENTE EFFETTI BIOLOGICI PER IRRADIAZIONE ACUTA > 1 Sv Nausea (from necrosis of the cells of the digestive tract) may occur and mild leukopenia and anemia occur and regress spontaneously within 6 months 1-2 Sv Nausea, anemia, leukopenia, thrombocytopenia (resulting from effects on the bone marrow), ease of infection due to leukopenia. 2 ~ 5 Sv Vomiting, severe anaemia, thrombocytopenia, leukopenia, haemorrhages and oedema (due to damage to endothelial cells), hair loss, infections (due to leukopenia and damage to the barriers of entry - skin and gastrointestinal epithelium-) 4 Sv death 50% of cases 6 Sv Unlikely survival Those who manage to overcome acute irradiation sickness are still exposed to the risk of long-term effects, such as the onset of neoplasms (see next slide)  Tumors Leukemias Bone tumors Thyroid cancer Lung cancers CANCERS FROM RADIATION EXPOSURE FOR PROFESSIONAL USE SKIN CANCER (the first radiologists) LUNG CANCER (uranium mine workers) BONE CANCER, especially the jaw (watch dial painters) Radium Girls The map represents the mapping of the areas at risk of radon in Veneto: the Region has defined risk areas as those in which at least 10% of homes are estimated to exceed the reference level of 200 Bq/m3, intended in terms of average annual concentration. The figure shows, grouped into classes, the percentages of dwellings with radon The Becquerel is the unit of measurement adopted by the concentrations above 200 Bq/m3: areas at risk International System to express the activity of a radioactive are those characterized by dark red and brown substance, i.e. the number of decays that occur in 1 second in a material. colors.  RADON is a natural radioactive gas emitted by the decay of radium, generated in turn by the decay of uranium, present in rocks, soil and building materials. Colorless, it is extremely volatile. As a dissolved gas, it is also transported over great distances from the place of formation and can be present in groundwater. The path that generally takes to reach the inside of the houses is the one that passes through cracks and small holes in the cellars and in the basement. The interaction between building and site, the use of particular building materials, and building types are therefore the most relevant elements for the assessment of the influence of Radon on the indoor air quality of homes and buildings in general.  ULTRAVIOLET RADIATION 1 Ultraviolet radiation makes up about 10% of the light emitted by the Sun and is also produced by special lamps (Wood's lamps or UV-A lamps (1) and germicidal lamps (2)). They are radiations with an energy lower than 10 eV and therefore are not able to ionize the molecules against which they collide. However, they are able to EXCITE, i.e. to cause a transition 2 of electrons from a ground state (stable) to a state with a higher energy content. The transition between the two states (between two orbitals) does not occur randomly because the various levels have a quantized energy, so an electron will pass from one orbital to another, only if the energy that is supplied to it corresponds exactly to the difference in energy between the two levels.  USO DELLA LAMPADA DI WOOD IN DERMATOLOGIA In medicina la lampada di Wood può essere impiegata per evidenziare alcune infezioni da funghi, come la pitiriasi versicolor da Malassezia furfur, nel qual caso si evidenzia una fluorescenza gialla, e diverse altre malattie a carico della pelle, ad esempio la vitiligine, con fluorescenza bianca. UV RADIATION UV can be divided into different bands, differently defined according to the fields of study. The most immediate breakdown is: Near or near UV (400-200 nm) and extreme UV (200-10 nm). When considering the effect of UV rays on human health, the range of UV wavelengths is typically divided into: UV-A (400-320 nm), UV-B (320-290 nm) and UV-C (290-200 nm).  Most of the UV rays that reach the Earth are UVA, because all of the UVC band and 90% of the UVB band are absorbed by the atmosphere. UV radiation levels are highest as altitude increases (10-12% per 1000 m) and sun height, and as latitude and cloud cover decrease. At sea level, most is infrared and a small part is UV; The solar spectrum is as follows: - 58% Infrared - 40% Visible - 2% UV  UV DAMAGE WITH THE INVOLVEMENT OF PHOTOSENSITIZERS The most important sensitization mechanism in UVA occurs through the formation of oxygen radicals, such as singlet oxygen, which primarily attacks the guanine base, and hydroxyl radicals, which are particularly efficient in producing cuts in DNA. 8-oxyguanine is the main photoproduct resulting from the sensitized action of UVA on DNA. This photoproduct is highly mutagenic; given the preferential incorporation of adenine as a complement to the modified base, its presence generally leads to a G->T transversion, but other types of mutations are also possible. Other damages are lipid peroxidation and oxidation of amino acids. Through photosensitizer-mediated mechanisms (but also direct mechanisms) covalent bonds between DNA and proteins can be formed. Bonds are formed mainly between thymine and lysine, but purine bases can also bind to alanine, leucine, and serine.  UV PENETRANCE INTO THE SKIN the epidermis is a powerful filter against UVC radiation; UVB radiation does not exceed a depth of 70 mm, while the epidermis is relatively transparent to UVA radiation, which is largely absorbed by the dermis 30 m and, in a small percentage, is able to reach the subcutaneous tissue. 70 m The absorption properties of the epidermis depend essentially on the chromophores present in its structures. Nucleic acids and aromatic amino acids are the strongest absorbers in UVB and UVC; melanins represent the most important endogenous shield contained in the epidermis. The absorbency of skin tissues as a whole varies considerably depending on the color of the skin: for example, the absorption of radiation at 300 nm is about twice as high in black skin than in white skin. Skin cancers can be caused by both UVA and UVB UVA is the main culprit of aging. BASALIOMA UVA↑ oxidizing power and ↓ genotoxic power UVB and UVC ↓ oxidizing power and ↑genotoxic power MELANOMA Frequency of skin cancers Melanoma is the most dangerous of the three because it tends to metastasize THE CARCINOGENICITY OF UVB IS ATTRIBUTED TO THE FORMATION OF THYMINE DIMERS IN DNA Nucleotide Excision Repair (NER) is responsible for repairing (among others) damage caused by massive helix distortion, such as thymine dimers caused by UV light. Compared to Base Excision repair (BER) which is more specific to individual bases, NER is able to repair larger regions of DNA. Riparazione per escissione dei nucleotidi, NER (Nucleotide Excision Repair) Ad alta esposizione ad UV la capacità del sistema riparativo NER è sopraffatta → errori non riparati e in alcuni casi cancro Soggetti con mutazioni nel sistema NER: XERODERMA PIGMENTOSUM (XP, recessivo) Tanning booths mainly emit UVA rays. High-pressure sunlamps used in tanning salons emit UVA doses of up to 12 times that of the sun. It's no surprise that people who use tanning salons are 2.5 times more likely to develop squamous cell carcinoma and 1.5 times more likely to develop basal cell carcinoma. According to a study a few years ago, exposure to tanning beds by young people increases their risk of melanoma by 75%.