PDF 4.2 Radiation Damage in Biological Systems
Content
A Look at Nuclear Science and Technology
Larry Foulke
Radiation and Realism 4.2 Radiation Damage in Biological Systems
Let’s Review Ionization
• All three radiation types are capable of ionizing target atoms in materials. • What were the three types of radiation? • Charged particles (protons, electrons, fission products, alpha particles) • Electromagnetic radiation (gamma rays, X-rays) • Neutrons
Nuclear Engineering Program
Let’s Review Ionization
• All three radiation types are capable of ionizing target atoms in materials. • Ionization events are the root cause behind ALL observable effects of radiation.
– Ionization reactions damage materials by breaking chemical bonds and disrupting normal chemical processes (material embrittlement, biological damage, etc.).
• The rate of ionization (damage) depends on the type and energy of the radiation, as well as the constituent atoms in the target material.
Nuclear Engineering Program
Ionizing Radiations
• Is radiation that contains enough energy to remove one or more electrons from an atom or molecule.
– All charged particles are ionizing. – Only photons with an energy greater than the ionization energy of a given atom or molecule are considered ionizing. – Some molecules are affected by photons in the visible or UV range, but typically only X-rays and gamma rays are considered ionizing.
photon charged particle neutron
Nuclear Engineering Program
Image Source: See Note 1
Ionizing Radiations
• Neutrons do not have a charge and do not interact with the electron cloud so they are not able to directly cause ionizations. • However, neutron interactions with atomic nuclei can produce secondary particles that cause ionizations.
– Elastic collisions with light (H, C, O, N) nuclei cause the positively charged nucleus to recoil. – Inelastic collisions or nuclear absorptions produce ionizing γ rays. – Fission events produce positively charged fission fragments as well as ionizing γ rays.
Nuclear Engineering Program
• The number of ionization events that a single particle of radiation can produce is determined by the energy of the radiation. • The ionization density is determined by the LET.
---------------------------------------------------------Relative Relative Radiation Range LET ---------------------------------------------------------Alpha 1 10,000 Beta 100 100 Gamma 10,000 1 ---------------------------------------------------------Nuclear Engineering Program
Ionization Density
Ionization Density
Average Human Cell
neutron gamma ray x-ray alpha particle
Separation of ion clusters relative to size of a human cell (conceptualized)
Nuclear Engineering Program Image Source: See Note 2
Review of “Biology 101”
• An animal is an organized collection of organs, held together by connective tissue, whose functions are coordinated by a nervous system.
– Cells are the basic building blocks of life – Cells are grouped together by specialization into tissues – Tissues work together to form organs, which perform specific functions – Adult humans have approximately 7×1013 total cells of 210 different types
Nuclear Engineering Program
Cell Functions
• All cells perform certain basic tasks:
– Metabolism • Cells break down complex nutrient molecules to release energy that is used to enable biochemical reactions within the cell. – Protein Synthesis • Protein molecules take part in all biochemical processes in the cell. Each cell builds proteins required to perform the specialized tasks of the cell. – Reproduction • Cells reproduce by division, referred to as mitosis in eukaryotic cells.
• Every cell contains specialized organelles, which are responsible for performing these tasks.
Nuclear Engineering Program
Organelles
1. Nucleolus 2. Nucleus 3. Ribosome 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytoplasm 12. Lysosome 13. Centriole
Cell Biology 101
Every cell is 70-90% water
Nuclear Engineering Program Image Source: See Note 3
Cell Damage
• Ionization can disrupt any of the three major functions of cells:
– Metabolism
• Cell may not produce the energy that it needs and dies.
– Protein synthesis
• Cell may not create protein needed for cell survival. -or• Cell may not create protein required for its specialized task. Cell is alive but useless.
– Reproduction
• Cell may not reproduce, or may reproduce incorrectly. Cell remains alive and functioning, but is sterile.
Nuclear Engineering Program
Cell Damage
• Many ionizations within a single cell typically results in enough damage to disrupt metabolism or protein synthesis and immediately kill the cell. • For radiation damage, this requires a lot of energy to be deposited within a single cell:
– Direct radiation damage • High LET charged particles ionize biological molecules directly.
– Indirect radiation damage
• High-energy γ rays produce strongly oxidizing free-radicals by radiolysis. The free radicals then travel through the cell destroying molecules. Because cells are mostly water, indirect damage due to radiolysis of water is the most common mechanism.
Nuclear Engineering Program
Radiolysis of Water
Before Reaction
Possible Recombination Products
Free electron (Charged particle) H, H- or H+ (Free radical, and charged particles) Hydroxyl (Free radical) Hydrogen peroxide (Free radical) Oxygen Hydrogen Electron γ ray Hydroperoxyl (Free radical) Other (neutral) products: H2, O2, H2O
Nuclear Engineering Program Image Source: See Note 1
BAD
Traumatic Cell Death
• Cells have redundant features and many types of repair mechanisms to handle biochemical disruptions (otherwise we would never survive!). • Cell death typically requires hundreds of ionizations or oxidations within a single cell. • However, cell reproduction is much more sensitive to ionization / oxidation events. One or two events can disrupt the normal cell cycle.
Nuclear Engineering Program
What about radiation and DNA?
• Cells have redundant features and many types of repair mechanisms to handle biochemical disruptions (otherwise we would never survive!). • Cell death typically requires hundreds of ionizations or oxidations within a single cell. • In the human body, approximately 500,000 radioactive disintegrations occur every minute. (Luckey, Radiation Hormesis, 1991) • Every hour on the average, every cell in the human body undergoes approximately 8000 DNA-modifying events, independent of radiation. (Abelson, P.H.; Science, Vol. 265, 9 September 1994, p. 1507)
Nuclear Engineering Program
• DNA is organized into a double-helix shape, with nucleotide base-pairs between 2 phosphate backbones. • The DNA sequence is arranged into bands called genes. Each gene carries the recipe for one protein. • Humans have 23 pairs of chromosomes (one set from mom, one from dad). • Pollycove: “The body has about 100 trillion cells.” • Pollycove: “Each cell undergoes about 25,000 DNA alternations daily.”
DNA
Nuclear Engineering Program
Image Source: See Note 4
Radiation Dose Effects
• The amount of energy deposited in a material is referred to as radiation dose. • Chronic Dose
– Dose delivered over an extended period of time.
• Acute Dose
– Dose delivered over a short period of time. – An acute dose is generally more damaging than a chronic dose of the same size, because the body’s repair mechanisms have less opportunity to act.
Nuclear Engineering Program
Short-Term Radiation Effects
• Immediate Effects (hours to days)
Increasing Dose
– Skin reddening, inflammation – Immune suppression – Sterility – Blood chemistry changes – Loss of hair – Gastrointestinal syndromes – Central nervous system syndromes
Nuclear Engineering Program
Long-Term Radiation Effects
• Long term effects (months to years)
– Cancer / leukemia – Cataracts – Genetic defects – Blood disorders – Lifespan shortening
• Scientific consensus on high dose effects. • Lack of consensus on low dose effects.
Nuclear Engineering Program
Image Source Notes
1. Reprinted with permission from David Griesheimer, University of Pittsburgh. 2. Public domain: http://commons.wikimedia.org/wiki/File:Dia gram_human_cell_nucleus_no_text.png 3. Public domain: http://en.wikipedia.org/wiki/File:Animal_Ce ll.svg 4. Public domain: http://en.wikipedia.org/wiki/Dna
Larry Foulke
Radiation and Realism 4.2 Radiation Damage in Biological Systems
Let’s Review Ionization
• All three radiation types are capable of ionizing target atoms in materials. • What were the three types of radiation? • Charged particles (protons, electrons, fission products, alpha particles) • Electromagnetic radiation (gamma rays, X-rays) • Neutrons
Nuclear Engineering Program
Let’s Review Ionization
• All three radiation types are capable of ionizing target atoms in materials. • Ionization events are the root cause behind ALL observable effects of radiation.
– Ionization reactions damage materials by breaking chemical bonds and disrupting normal chemical processes (material embrittlement, biological damage, etc.).
• The rate of ionization (damage) depends on the type and energy of the radiation, as well as the constituent atoms in the target material.
Nuclear Engineering Program
Ionizing Radiations
• Is radiation that contains enough energy to remove one or more electrons from an atom or molecule.
– All charged particles are ionizing. – Only photons with an energy greater than the ionization energy of a given atom or molecule are considered ionizing. – Some molecules are affected by photons in the visible or UV range, but typically only X-rays and gamma rays are considered ionizing.
photon charged particle neutron
Nuclear Engineering Program
Image Source: See Note 1
Ionizing Radiations
• Neutrons do not have a charge and do not interact with the electron cloud so they are not able to directly cause ionizations. • However, neutron interactions with atomic nuclei can produce secondary particles that cause ionizations.
– Elastic collisions with light (H, C, O, N) nuclei cause the positively charged nucleus to recoil. – Inelastic collisions or nuclear absorptions produce ionizing γ rays. – Fission events produce positively charged fission fragments as well as ionizing γ rays.
Nuclear Engineering Program
• The number of ionization events that a single particle of radiation can produce is determined by the energy of the radiation. • The ionization density is determined by the LET.
---------------------------------------------------------Relative Relative Radiation Range LET ---------------------------------------------------------Alpha 1 10,000 Beta 100 100 Gamma 10,000 1 ---------------------------------------------------------Nuclear Engineering Program
Ionization Density
Ionization Density
Average Human Cell
neutron gamma ray x-ray alpha particle
Separation of ion clusters relative to size of a human cell (conceptualized)
Nuclear Engineering Program Image Source: See Note 2
Review of “Biology 101”
• An animal is an organized collection of organs, held together by connective tissue, whose functions are coordinated by a nervous system.
– Cells are the basic building blocks of life – Cells are grouped together by specialization into tissues – Tissues work together to form organs, which perform specific functions – Adult humans have approximately 7×1013 total cells of 210 different types
Nuclear Engineering Program
Cell Functions
• All cells perform certain basic tasks:
– Metabolism • Cells break down complex nutrient molecules to release energy that is used to enable biochemical reactions within the cell. – Protein Synthesis • Protein molecules take part in all biochemical processes in the cell. Each cell builds proteins required to perform the specialized tasks of the cell. – Reproduction • Cells reproduce by division, referred to as mitosis in eukaryotic cells.
• Every cell contains specialized organelles, which are responsible for performing these tasks.
Nuclear Engineering Program
Organelles
1. Nucleolus 2. Nucleus 3. Ribosome 4. Vesicle 5. Rough endoplasmic reticulum 6. Golgi apparatus 7. Cytoskeleton 8. Smooth endoplasmic reticulum 9. Mitochondrion 10. Vacuole 11. Cytoplasm 12. Lysosome 13. Centriole
Cell Biology 101
Every cell is 70-90% water
Nuclear Engineering Program Image Source: See Note 3
Cell Damage
• Ionization can disrupt any of the three major functions of cells:
– Metabolism
• Cell may not produce the energy that it needs and dies.
– Protein synthesis
• Cell may not create protein needed for cell survival. -or• Cell may not create protein required for its specialized task. Cell is alive but useless.
– Reproduction
• Cell may not reproduce, or may reproduce incorrectly. Cell remains alive and functioning, but is sterile.
Nuclear Engineering Program
Cell Damage
• Many ionizations within a single cell typically results in enough damage to disrupt metabolism or protein synthesis and immediately kill the cell. • For radiation damage, this requires a lot of energy to be deposited within a single cell:
– Direct radiation damage • High LET charged particles ionize biological molecules directly.
– Indirect radiation damage
• High-energy γ rays produce strongly oxidizing free-radicals by radiolysis. The free radicals then travel through the cell destroying molecules. Because cells are mostly water, indirect damage due to radiolysis of water is the most common mechanism.
Nuclear Engineering Program
Radiolysis of Water
Before Reaction
Possible Recombination Products
Free electron (Charged particle) H, H- or H+ (Free radical, and charged particles) Hydroxyl (Free radical) Hydrogen peroxide (Free radical) Oxygen Hydrogen Electron γ ray Hydroperoxyl (Free radical) Other (neutral) products: H2, O2, H2O
Nuclear Engineering Program Image Source: See Note 1
BAD
Traumatic Cell Death
• Cells have redundant features and many types of repair mechanisms to handle biochemical disruptions (otherwise we would never survive!). • Cell death typically requires hundreds of ionizations or oxidations within a single cell. • However, cell reproduction is much more sensitive to ionization / oxidation events. One or two events can disrupt the normal cell cycle.
Nuclear Engineering Program
What about radiation and DNA?
• Cells have redundant features and many types of repair mechanisms to handle biochemical disruptions (otherwise we would never survive!). • Cell death typically requires hundreds of ionizations or oxidations within a single cell. • In the human body, approximately 500,000 radioactive disintegrations occur every minute. (Luckey, Radiation Hormesis, 1991) • Every hour on the average, every cell in the human body undergoes approximately 8000 DNA-modifying events, independent of radiation. (Abelson, P.H.; Science, Vol. 265, 9 September 1994, p. 1507)
Nuclear Engineering Program
• DNA is organized into a double-helix shape, with nucleotide base-pairs between 2 phosphate backbones. • The DNA sequence is arranged into bands called genes. Each gene carries the recipe for one protein. • Humans have 23 pairs of chromosomes (one set from mom, one from dad). • Pollycove: “The body has about 100 trillion cells.” • Pollycove: “Each cell undergoes about 25,000 DNA alternations daily.”
DNA
Nuclear Engineering Program
Image Source: See Note 4
Radiation Dose Effects
• The amount of energy deposited in a material is referred to as radiation dose. • Chronic Dose
– Dose delivered over an extended period of time.
• Acute Dose
– Dose delivered over a short period of time. – An acute dose is generally more damaging than a chronic dose of the same size, because the body’s repair mechanisms have less opportunity to act.
Nuclear Engineering Program
Short-Term Radiation Effects
• Immediate Effects (hours to days)
Increasing Dose
– Skin reddening, inflammation – Immune suppression – Sterility – Blood chemistry changes – Loss of hair – Gastrointestinal syndromes – Central nervous system syndromes
Nuclear Engineering Program
Long-Term Radiation Effects
• Long term effects (months to years)
– Cancer / leukemia – Cataracts – Genetic defects – Blood disorders – Lifespan shortening
• Scientific consensus on high dose effects. • Lack of consensus on low dose effects.
Nuclear Engineering Program
Image Source Notes
1. Reprinted with permission from David Griesheimer, University of Pittsburgh. 2. Public domain: http://commons.wikimedia.org/wiki/File:Dia gram_human_cell_nucleus_no_text.png 3. Public domain: http://en.wikipedia.org/wiki/File:Animal_Ce ll.svg 4. Public domain: http://en.wikipedia.org/wiki/Dna
