MAMMALIAN RADIATION BIOLOGY COURSE

1. MAMMALIAN RADIATION BIOLOGY COURSE Lecture 1 INTERACTION OF RADIATION WITH BIOLOGICAL SYSTEMS

2. TOPICS COVERED IN THIS LECTURE • Definition of ionizing radiation • Types of ionizing radiation and non-ionizing radiation • Definition of LET and quality of ionizing radiation • Generation of free radicals • Direct and indirect action of ionizing radiation

3. Definition of ionizing radiation

4. Radiation Biology A study of the action of ionizing radiation on living things LD/50 = 4 Gy 4 Gy = 67 calories 67 calories = 3 ml sip of 60°C coffee 30-100 Trillion Cells at Risk • Different Cell Types • Different Cell Cycle • Different Cell Targets

5. RADIATION Radiation is the term given to the energy transmitted by means of particles or waves. It can beionizingor non-ionizing

6. IONIZING RADIATION The absorption of energy from radiation in biologic material may lead to excitation or to ionization. If the radiation has sufficient energy to eject orbital electrons from the atom or molecule, the process is called ionization and that radiation is said to be Ionizing Radiation

7. The important characteristic of ionizing radiation is the localized release of large amounts of energy. The energy per ionizing event – 33 eV – well enough to break a chemical bond (ex. C=C bond is 4.9 eV).

8. Definition of ionizing radiation • Types of ionizing radiation and non-ionizing radiation • Definition of LET and quality of ionizing radiation • Generation of free radicals • Direct and indirect action of ionizing radiation

9. IONIZING RADIATION X-rays and γ-rays do not differ in nature or in properties, only in the way they are produced X-rays (produced extra-nuclearly) γ-rays (produced intra-nuclearly) • Electromagnetic • Particular Electrons Protons α-Particles Neutrons Deuterons Heavy charged particles

10. X-rays are electromagnetic waves λ - wavelength ν - frequency c - velocity λν=c All forms of electromagnetic radiation have the same velocity, but different wavelength, and therefore different frequencies

11. Like X-rays, radio waves, radar, radiant heat, laser and visible light are forms of electromagnetic radiation. They have the same velocity but different wavelengths. The Electromagnetic Spectrum For example, radio wave have a wavelength of 300m; visible light - 5x10-5; X-rays - 1x10-8cm.

12. X-rays may be thought of as electromagnetic waves and-alternatively- as streams of photons, or “packets” of energy Each energy packet contains an amount of energy equal to E=hν, wherehis Planck’s constant and ν is the frequency If a radiation has a long wavelength, it has a small frequency (λν=c), and so the energy per photon is small. Conversely, radiation with short wavelength will have a large frequency and hence the energy per photon is large. In their biological effects, electromagnetic radiations are considered to be ionizing if they have a photon energy in excess of 124 eV, which corresponds to a wavelength shorter than about 10-6 cm.

13. Electromagnetic Spectrum

14. Electromagnetic Spectrum

15. The biologic effect of radiation is determined by the photon size of the energy, not by the amount of energy absorbed. Lethal dose of 4Gy corresponds to only 67 cal of the total energy absorbed Excess temperature (0C) = 60 - 37 = 23 Volume of coffee consumed to equal the energy in the LD/50/60 = 67 23 = 3 ml = 1 sip Mass = 70kg LD/50/60 = 4Gy Energy absorbed = 70 x 4 = 280 joules 280 = 67 calories 4.18 Mass = 70 kg Height lifted to equal the energy in the LD/50/60 = 280 70 x 0.0981 = 0.4 m (16 inches)

16. Particulate Radiations Electrons Protons α-Particles Neutrons Deuterons Heavy charged particles These types of radiation occur in nature and also are used experimentally, in radiation therapy and diagnostic radiology

17. Alpha Radiation () • Nuclei of helium atoms • 2 protons and 2 neutrons • Heavy, slow, +2 charge • Can be accelerated in electrical devices similar to those used for protons • High linear energy transfer (LET) • Low penetrability • They are also emitted during the decay of heavy naturally occuring radionuclides: 210 206 4 Po  Pb + He 84 2 82

18. Decay of a Heavy Radionuclide by the Emission of an α-particleThe emission of an α-particle (two protons and two neutrons) decreases the atomic number by two and the mass number by four. Note that the radium has changed to another chemical element, radon, as a consequence of the decay.

19. Beta Radiation () • Electron emitted from nucleus • Light, Fast, -1 charge • Can be accelerated to high energies in betatron or linear accelerator. Widely used in cancer therapy • Can travel several feet in air and has a medium penetrability • The range of beta particle is considerably greater than an alpha particle • Beta particle may transfer energy through ionization, excitation and it can produce a Bremsstrahlung radiation (X-rays)

20. Alpha particles and beta particles are cosidered directly ionizing because they carry a charge and can, therefore, interact directly with atomic electrons through coulombic forces (i.e. like charges repel each other; opposite charges attract each other).

21. Neutrons (n) • Neutral particle • Classified by energy: • Thermal neutrons – E < 1eV • Fast neutrons – E > 10 keV • Indirectly ionizing (no electrical charge). Ionization is caused by charged particles, which are produced during collisions with atomic nuclei • Neutrons are also emitted as byproducts of fission of heavy unstable radioactive atoms. With the exception of 209 Bi each nucleus with an atomic number greater than 82 is unstable. • Neutrons interaction depends on the neutron energy and the material of the absorber: Scattering: elastic and inelastic; capture; spallation

22. Various trajectories and target Photon Neutron Alpha particle

23. Interaction of photons with matter • Photons have zero mass, zero charge, and a velocity that is always • “c”, the speed of light; • They do not steadily lose energy via coulombic interactions with • atomic electrons as do charged particles; • Photons travel considerable distance before transferring the photon • energy to electron energy; • Photons are far more penetrating than charged particles of similar • energy.

24. Absorption of an X-ray photon by the Compton processThe process by which X-ray photons are absorbed depends on the energy of the photons and the chemical composition of the absorber. At high energies (100 keV-10 MeV) characteristic of a cobalt-60 unit or a linear accelerator used for radiotherapy, the Compton process dominates Part of the photon energy is given to the electron as kinetic energy. The photon proceeds with reduced energy

25. Absorption of an X-ray photon by the photoelectric processThe photon gives up its energy entirely; the electron is ejected from the atom. The vacancy is filled either by an electron from an outer orbit or by a free electron from outside the atom. The change in energy is emitted as a photon of characteristic X-rays. • It is a predominant mode of • photon interaction at: • relatively low photon energies • high atomic number Z

26. Absorption of neutronselastic collision Neutrons lose their energy by elastic collision with nuclei of similar mass. In soft tissues interaction of a fast neutron with the hydrogen nuclei (protons) is the dominant process of energy transfer. Part of the energy of the neutron is given to the proton as kinetic energy. Deflected neutron proceeds with reduced energy.

27. At energies above 6MeV inelastic scattering contributes to energy loss in the absorbing material. The neutron may interact with carbon or oxygen nucleus to produce three of four α-particles. These are known as spallation products which are very important at higher energies. Inelastic scattering

28. NON-IONIZING RADIATION • Can cause excitation of atoms where electrons jump to higher atomic energy levels but are not removed from the atom: • UV light • - Lasers • Microwave • Radio waves • - Infrared Waves

29. LASER - Light Amplification by Stimulated Emission of Radiation • Light - describes all types of energy emitted from a laser; visible and invisible • Amplification - of electromagnetic energy necessary to produce a very high intensity laser beam • Stimulated Emission - process that occurs at the atomic level, by which electromagnetic energy is amplified • Radiation - describes how energy is transferred. Does NOT refer to x-rays or gamma rays. • CHARACTERISTICS OF LASER LIGHT • Monochromatic - when laser light is passed through a prism, no separation occurs • Directional - all laser energy travels in the same direction • Coherent - rays of laser energy travel together without interfering with one another

30. Interactions of the Laser with Matter 1. Can be absorbed, reflected or transmitted 2. Reflection of laser energy from material surfaces occurs in 2 ways - Specular - interacts with smooth surfaces and maintains most of the original beam of energy - Diffuse - interacts with coarse surfaces and disperses the energy in many directions 3. The further laser energy travels within a given material, the more likely the energy will be absorbed within the material - The laser wavelength and the material with which it interacts determine what percentage of laser energy will be absorbed, reflected or transmitted

31. Ultraviolet Radiation

32. Definition of ionizing radiation • Types of ionizing radiation and non-ionizing radiation • Definition of LET and quality of ionizing radiation • Generation of free radicals • Direct and indirect action of ionizing radiation

33. Linear Energy Transfer (LET) is the energy transferred per unit length of the track. Unit for LET is keV/µm-kiloelectron volt per micrometer of unit density material. L=dE/dl, where dE-energy transferred by a charged particle of specified energy in traversing a distance of dl

34. Optimal Linear Energy Transfer (LET): Radiation with LET of 100 keV/µM is the most efficient in producing biological damage. The average separation between ionizing events coincides with the diameter of the DNA double helix

35. Sparsely ionizing track of a fast electron in a cloud chamber Densely ionizing track of an alpha particular in a cloud chamber The deposition of energy of different types of radiation • A 10-MeV proton, typical of the recoil protons produced by high-energy neutrons used for radiotherapy. The track is intermediate in ionization density. • A 500-keV proton, produced by lower energy neutrons (e.g., from fission spectrum) or by higher-energy neutrons after multiple collisions. The ionizations form a dense column along the track of the particle. • A 1-MeV electron, produced for example, by photons of cobalt-60- -rays. The particle is very sparsely ionizing. • A 5-keV electron, typical of secondary electrons produced by x-rays of diagnostic quality. This particle is also sparsely ionizing but a little denser than the higher-energy electron.

36. The deposition of energy of different types of radiation dispersion of energy air tissue high LET (, n, ~) greater radiotoxicity incident radiation low LET (, x, ~) LET = linear energy transfer

37. Typical Linear Energy Transfer Values

38. Definition of ionizing radiation • Types of ionizing radiation and non-ionizing radiation • Definition of LET and quality of ionizing radiation • Generation of free radicals • Direct and indirect action of ionizing radiation

39. Radiation interaction with water The cell is composed of 80% water. The ultimate result of radiation interaction with water molecule is the formation of an ion pair and free radicals. Free radicals have an unpaired electron in their outer shell, a state which confers a high degree of reactivity. radiation HOH HOH+ + e- HOH + e- HOH- H+ + OH•* HOH+ HOH- OH- + H• Ion pair (H+, OH-) HOH Free Radicals (H•, OH•)

40. Free radicals initiate chemical reactions that lead to the production of damage via indirect action in the cell. The following outline summarizes the general sequence of events that occurs in the cell via indirect action: X-ray photon fast electron (e) ion radical free radical chemical changes biologic effect

41. Definition of ionizing radiation • Types of ionizing radiation and non-ionizing radiation • Definition of LET and quality of ionizing radiation • Generation of free radicals • Direct and indirect action of ionizing radiation

42. When ionizing radiation interacts with a cell, ionizations and excitations are produced either in critical biological macromolecules (e.g. DNA) or in the medium in which the cellular organelles are suspended (e.g. water, HOH). Based on the site of these interactions, the action of radiation on the cell can be classified as either direct or indirect.

43. Electromagnetic radiations such as X- and gamma-rays are indirectly ionizing. In indirect action the critical site is damaged by reactive species produced by ionizations elsewhere in the cell, which in turn damage the target

45. Direct action dominates for more densely ionizing radiations such as neutrons because the secondary charged particles produced result in a dense column of ionizations more likely to interact with DNA.

46. Sequence of Events in Indirect Action T1/2 in sec Incident X-ray photons  10-15 Fast electrons  10-5 Ion radicals  10-5 Free radicals  Macromolecular changes from breakage of chemical bonds  Biological effects days - cell killing generation - mutation years - carcinogenesis