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Radiobiology Basics and Radiation principle
- 1. Radiobiology Basics นพ. เฉลิมภักดิ์ศุภคติธรรม Chalermpak@nmu.ac.th
- 2. เนื้อหาโดยสังเขป • Introduction • Physicaland chemical effect of radiation • Cell survival curve • Radioprotectors and radiosensitizers • Effect of radiation on molecules and cells
- 3. Sea of radiationwe live in • Scientists have studied radiation for over 100 years • Radiation has always been around us as a part of nature. Cosmic radiation (from outer space) at sea level (26 mrem: millirem) The annual average dose per person from all natural and man-made sources is about 620 mrems. • The U.S. Nuclear Regulatory Commission (NRC) standards up to 5,000 mrem per year (Work with and around radioactive material) • *The reduction in life expectancy from a dose of 1 mrem is about 1.2 minutes. 1 mrem equivalent to the reduction in life expectancy from crossing the street three times, taking three puffs on a cigarette, or consuming 10 extra calories (for a person who is overweight). Terrestrial Radiation: different concentrations of uranium and thorium in soil. Internal Radiation: radioactive material inside their bodies (may be from soils)
- 4. รังสี Definition • Radiationis an energy in the form of electro-magnetic waves or particulate matter, traveling in the air. • A type of radiation that is able to disrupt atoms and molecules on which they pass through, giving rise to ions and free radicals. รังสีก่อประจุ Ionizing Radiation รังสีไม่ก่อประจุ : ช่วงตํ่าของแถบ EM waves
- 5. ELECTROMAGNETIC RADIATIONS Photon E= h(energy = Planck’s const x frequency) = hc/ (c = speed of light, = wave length) 10-9 10-8 10-7 10-6 10-5 10-4 10-3 10-2 10-1 1 10 102 103 104 rays X-rays U.V. v i s i b l e InfraRed Radio Waves Microwaves Short Waves T.V. Radio Radar IONIZING RADIATION NON-IONIZING RADIATION (cms) E (eV) 1.24x107 1.24x102 1.24x10-13
- 6. กัมมันตภาพรังสี Radioactivity • Ifa nucleus is unstable for any reason, it will emit and absorb particles. There are many types of radiation and they are all pertinent to everyday life and health as well as nuclear physical applications. • การแผ่รังสีได้เองอย่างต่อเนื่องของธาตุกัมมันตรังสี Radiobiology • Basic principles of physics and biology: action of ionizing radiation on biological tissues and living organisms
- 7. Types of Radiation Inspiredby various images by IAEA. UNSCEAR, etc. X-ray or รังสีแอลฟา อันตรายถ้าสูดดม กิน หรือเข้าทางแผลเปิด: Positively charged, helium nucleus
- 8. Man-Made Radiation • Diagnosticradiology (X-rays) : The largest source of man- made radiation • Nuclear medicine (Radiopharmaceuticals) • Radiotherapy (Co-60)
- 9. วัดปริมาณ • รังสีที่แผ่ออกมา หน่วยเดิมคูรี (Ci) หน่วยสากล เบคเคอเรล (Bq) 1 Ci = 37000 ล้าน Bq • รังสีที่คนได้รับหรือที่ดูดซับโดยเนื้อเยื่อ หน่วยเดิม แรด (Rad = Roentgen absorbed dose) หน่วยสากล เกรย์(Gy = Gray) 100 Rad= 1 Gy • รังสีสมมูล (ความเสี่ยงสุขภาพ จากรังสี) หน่วยเดิม (rem = Roentgen equivalent in man) หน่วยสากล ซีเวิร์ต (Sv: Sievert) 100 rem = 1 Sv
- 10. Effects of ionizingradiation on atom Ionization Excitation Also kinetic energy of non-ionizing radiation to raise the thermal energy of an outer shell electron (Excitation with emission)
- 11. Direct action of ionizingradiation Ionizing radiation + RH R- + H+ OH I R – C = NH imidol (enol) O II R – C = NH2 amide (ketol) Tautomeric shifts Bond breaks
- 12. e- X ray rayP+ O H H OH- H+ Ho OHo Indirect action of ionizing radiation (free radicals or highly reactive species) (ionization) Radiolysis Short life of free radicals (10-10sec), only those formed in water column of 2-3 nm around DNA Indirect action can be modified by chemical sensitizers or radiation protectors
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- 14. รางวัลโนเบลสาขาสรีรวิทยาหรือการแพทย์(พ.ศ. 2489) The NobelPrize in Physiology or Medicine 1946 • "for the discovery of the production of mutations by means of X-ray irradiation.“ Carcinogenic effects of X-rays Using hereditary characteristics fruit flies • Use for benign conditions has been limited since • The Nobel Prize in Physiology or Medicine 1946. NobelPrize.org. Nobel Prize Outreach AB 2021. Wed. 22 Jul 2021. <https://www.nobelprize.org/prizes/medicine/1946/ summary/>
- 15. DNA restoration failure UnrejoinedDNA double strand breaks Incorrect repair of DNA damage Cytotoxic effect Mutations
- 16. Classification of radiations •Linear energy transfer (LET) is used for defining the quality of an ionizing radiation beam. Linear rate of energy absorption by the absorbing medium as the charged particle traverses the medium. dE/dl (dE = the average energy locally imparted to the medium / dl = in traversing a distance of dl) keV/m • In contrast to the stopping power (Focus energy loss by a charged particle moving through a medium) MeV/cm Radiation LET keV/m 1 MeV -rays 100 kVp X-rays 20 keV -particles 5 MeV neutrons 5 MeV particles 0.5 6 10 20 50
- 17. Relation between linearenergy transfer (LET) and type of action Direct action is predominant cause of damage with high LET radiation, e.g. alpha particles and neutrons Indirect action is predominant (About 2/3) with low LET radiation, e.g. X and gamma rays
- 18. The stage ofaction of ionizing radiation Physical stage The transfer of kinetic energy from ionizing radiation to atoms or molecules leads to excitation and ionization of these atoms or molecules 10 – 18 – 10 – 15 seconds Physic-chemical stage The displace of absorbed energy of ionizing radiation into molecules and between them. Formation of free radicals 10 – 14 – 10 – 11 seconds Chemical stage Reactions between free radicals, reactions between free radicals and intact molecules. Formation of molecules with abnormal structure and function 10 – 6 – 10 – 3 seconds Biological stage Formation of injures on all levels – from cellular structures to organism and population. Development of processes of biological damage and reparative processes Seconds – years
- 19. Cell survival curves •Several factors may contribute to less radio-sensitive cells: Removal of oxygen to create a hypoxic state (Especially in low level LET) Adds a chemical radioprotectors for free radical scavengers Use of low dose rates or multi-fractionated irradiation Synchronization of cells in the late S phase of the cell cycle
- 20. Relative Biological Effectiveness(RBE) Dose of standard radiation required to produce an effect Dose of test radiation required to produce the same effect = S.F. 1.0 0.1 0.01 0.001 DOSE Gy High LET Low LET Physical Dose = Biological Dose S.F. = surviving fraction Standard = historically 250 kVp x-rays Now use: cobalt-60 gamma rays
- 21. Linear Energy Transfer(LET keV/m) RELATIVE BIOLOGICAL EFFECTIVENESS (for cell kill) 1000 100 10 1 0 2 4 6 8 RBE Diagnostic X-rays Fast Neutrons Alpha Particles overkill 0.1 Co-60 gamma rays 0 1 2 3 4 OER OER OER is the inverse of RBE because OER depends considerably on the indirect action of ionizing radiation RBE is maximal when the average distance between ionization events = distance between DNA strands = 2nm RBE and oxygen enhancement ratio
- 22. RADIOPROTECTORS AND RADIOSENSITIZERS • Somechemical agents may alter the cell response to ionizing radiation, either reducing or enhancing: Radioprotectors: reduce indirect effects of radiation by scavenging the production of free radicals. Radiosensitizers: promote both the direct and indirect effects of radiation
- 23. Tissues and livingorganisms • All living entities made up of protoplasm Inorganic and organic compounds in water • The smallest unit of protoplasm independently exists The cell => cytoplasm, nucleus Somatic cells or germ cells (sperm or egg) Mitosis or meiosis (Half of the Chromosome) • Groups of cells => tissue • Groups of tissues => organ • Groups of organs => organ system = organism
- 24. Effect of irradiationon cells • First, standard physical effects between radiation and the atoms or molecules of the cells • Then possible biological damage to cell functions • Mainly effects when damage to the DNA other sites damage may also lead to cell death • Surviving cell (Maintains reproductive integrity and proliferates into a large number of progeny)
- 25. Somatic cells • Stemcells Self-perpetuate and produce cells for a differentiated cell population 2 Gy required to typically destroy cell function • Transit cells In movement to another population • Mature cells Fully differentiated and usually no mitotic activity 100 Gy required to destroy cell function
- 26. Possible outcomes No effect Permeabilitychanges: may increase or decrease permeability Interference of function: e.g. decreased motility Division delay: The cell is delayed in going through division Apoptosis: The cell programmed to die Reproductive failure: The cell dies when attempting the mitosis Genomic instability: Delay in cell growth and division, shorten life Mutation: The cell survives but contains a mutation Transformation: The mutation => transformed phenotype and possibly carcinogenesis (May takes years) Bystander effects: An irradiated cell may send signals to neighboring unirradiated cells and induce genetic damage Adaptive responses: The irradiated cell becomes more radio‐ resistant Fate of irradiated cell Radiation Oncology Physics: A Handbook for Teachers and Students
- 28. Study materials • EricJH, Giaccia AJ. Radiobiology for the Radiologist. Lippincott Williams & Wilkins, 2018 • Suntharalingam N, Podgorsak EB, Hendry JH. Radiation Oncology Physics: A Handbook for Teachers and Students. Vienna: IAEA publication, 2005. • Kumar V, Abbas AK, Aster JC. Robbins and Cotran: Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier Saunders, 2021.
- 29. 1. Electromagnetic radiationis considered ionizing if its photon energy is greater than • 1.24 eV • 12.4 eV • 124 eV • 1.24 keV #3 – this is sufficient to break bonds in biological molecules
- 30. 2. The lifetimeof free radicals is roughly about • 0.001 (10 exp-3) seconds • 0.000001 (10 exp-6) seconds • 0.000000001 (10 exp-9) seconds • 0.000000000001 (10 exp-12) seconds
- 31. 3. What isthe S.I. (Système international d'unites) unit of absorbed radiation dose? • Becquerel • Roentgen • Sievert • Gray
- 32. 4. Which ofthe following is not charged particle? • Heavy ion • Electron • Neutron • Proton
- 33. 5. Which ofthe following is TRUE about Linear Energy Transfer? • It shows an inverse correlation with the oxygen enhancement ratio • It is a measure of the biological effectiveness of ionizing radiation • It is maximum at a relative biological effectiveness of 150 MeV/cm • It is measured in keV/micrometer