1. Radiation Biology
RADL 70
Kyle Thornton

2. Definition of Radiation Biology
Joins two branches of science to study the effects of radiation upon living matter
Radiation physics
The spread of energy through space
Biology
The study of living organisms
Most effects begin at the cellular level
All radiation injuries to tissue, organs, fetus, and entire body began from an injury to a cell

3. How Does Ionizing Radiation Do Harm?
It damages by removing electrons the atoms that compose the molecular structures of living systems
X and gamma rays can transfer energy to orbital electrons in their path
Alpha particles strongly attract negative electrons as they pass by
This alters the chemical bonds of the atom, changing its composition or structure
Different types of atoms unite through chemical bonds to form molecules
Molecules have specific functions
Altering the structure of the atom alters the moleculecular structure and its function

4. Linear Energy Transfer
The average amount of energy deposited per unit length of travel
Measured in units of keV per micron
The amount of ionization produced is affected by the amount of energy absorbed
Chemical and biological effects are determined by the degree of ionization that takes place within the tissue

5. Linear Energy Transfer
Low LET radiations
From x or gamma rays
Short wavelength, high energy waves
Sparsely ionizing
Randomly interact
They do not give up their energy quickly
Damage is usually caused indirectly
Free radicals are formed
Occasionally may cause single-strand breaks in one side of the DNA ladder
Damage is usually sublethal
Repair enzymes reverse the damage

6. Linear Energy Transfer
High LET radiation
From particles that do possess mass and charge
Alpha particles, particles released from interactions between neutrons and atoms
Lose energy more rapidly than x or gamma rays
Produce more ionization per unit length of travel
Their energy is exhausted sooner than that of an x or gamma ray

7. Linear Energy Transfer
Radiation of a high LET is far more likely to do damage than that of a low LET
Damage potential is greatest when a radionuclide has been ingested, planted, inhaled, or injected into the body
The damage done by high LET is usually irreparable
High LET radiation is far more likely to interact with DNA than low LET radiation

8. Electron/Alpha Particle Damage Comparison

9. Relative Biological Effectiveness
Biologic damage increases as LET increases
RBE is the ability of radiation with different LET to produce a biologic reaction

10. Oxygen Enhancement Ratio
The ratio of radiation damage done when oxygen is present compared to the amount when it is not
Cells that are normally hypoxic are less responsive to cells are that are highly oxygenated
This is only important when high doses outside the realm of diagnostic are used
This impact is very important in radiation therapy procedures

11. Direct Action
Biologic damage occurs from interaction between radiation and a master molecule
DNA, RNA, enzymes, and proteins
Occurs from photoelectric and Compton interaction
This results in breakage of the macromolecule’s chemical bonds
This will result in a malfunction of that particular molecule
This sets off a biologic domino effect

13. Indirect Action
The byproduct of radiation interacted with the macromolecule, not the radiation itself
Radiolysis of water is one of the main precursors of indirect action

14. Indirect Action

15. Indirect Action: Radiolysis of Water
X-ray photons are highly likely to interact with water molecules in the body
This interaction creates an ion pair
A water molecule with a positive charge HOH+
An electron - e-
One of several reactions might occur

16. Reaction I
The positively charged water molecule recombines with an electron
A stable water molecule is reformed
No damage is done

17. Reaction II The electron joins with a water molecule
A negative water ion is formed
The positive and negative water molecules are unstable
These can break apart into smaller molecules
Free radicals can be formed by this breakup
These are atoms that have no net electrical charge
These objects are highly reactive and can do cellular damage

18. Reaction III
Two of these free radicals can recombine to form hydrogen peroxide
This is highly toxic to a cell
About two-thirds of all biologic damage is caused by the two latter reactions

19. Another way to look at it…

20. News Flash!!!
Midterm exam takes place next meeting
Be ready

21. Effects on DNA Macromolecules
Point mutation
Ionizing radiation that ruptures the chemical bond of a macromolecule severing one of the sugar-phosphate chain siderails of the DNA ladder (Single-strand break)
Gene mutations may result
These can occur with low-LET radiation
Repair enzymes can reverse this damage

22. Double Strand Breaks
One or more breaks in each of the two sugar-phosphate chains
Not repaired as easily as single strand breaks
More common with high LET radiation

23. Cleaved Chromosomes
Two interactions hit on each side of the sugar phosphate chain
The macromolecule is broken in two
Each new portion contains an unequal amount of genetic material
This chromosome can then divide into defective daughter cells
This loss or change is known as a mutation

24. Let’s play mutation identification!

25. Effects of Ionizing Radiation Upon Chromosomes
If chromosomes are broken, two or more fragments are produced
Each fragment has a fractured extremity
These can join to another fractured extremity
These new formations are known as an aberration

26. Restitution – No Visible Damage

27. Deletion

28. Broken-end
Rearrangement

29. Broken End Rearrangement

30. DNA Mutations

32. Target Theory
Cell death will occur if the master molecule in that cell is inactivated by radiation exposure
This theory is used to explain cell death and nonfatal cell abnormalities caused by radiation exposure

33. Target Theory

34. Characteristics of Radiation Mutation
If the mutation is genetic, it may be expressed in future generations
If it is somatic, it holds possible consequences for the individual only
Radiation effects are non-specific
There are no radiounique effects
Most mutations are undesirable
Mutagenic effects are probably cumulative
A threshold exists

35. Cellular Effect of Irradiation
Instant death
Occurs when a volume is irradiated with 1000 Gray of x or gamma ray in a period of seconds or a few minutes
Radiation doses this high do not occur in the diagnostic or therapeutic ranges

36. Cellular Effect of Irradiation
Reproductive Death
Occurs from a dose of 1 – 10 Gray
The cell does not die, but becomes sterile
The cell will continue to metabolize and synthesize nucleic acids and proteins
Transmission of damage to future generations is prevented

37. Cellular Effect of Irradiation
Interphase Death
Depends upon the radiosensitivity of the cell
This death interrupts a programmed occurrence in normal development

38. Cellular Effect of Irradiation
Mitotic Death
Occurs when the cell dies after one or more divisions
Can occur from very small doses

39. Cellular Effect of Irradiation
Mitotic Delay
Can occur from a dose of as little as 1 rad
The cell fails to divide on time
Interference of function
This can be temporary or permanent
The cell can recover and continue to function if repair enzymes are able to fix the damage

40. Cell Radiosensitivity
Cells vary in their degree of radiosensitivity
Radiosensitive cells include basal cells of the skin, intestinal crypt cells, and reproductive cells
Radioinsensitive cells include brain, muscle, and nerve cells
Radiosensitivity varies from one tissue or organ to another

41. Cell Radiosensitivity
Other factors
LET
Presence of oxygen
Cancer cells are often hypoxic
Patients often undergo hyperbaric oxygenation to oxygenate cancer cells
This makes them more sensitive to radiation

42. Law of Bergonié and Tribondeau
Experimented on rabbit testicles
Their conclusion:
These cells are most radiosensitive by virtue of these factors:
Least maturity
Least specialization or differentiation
Greatest reproductive activity
Longest mitotic phases
True for all cells in the human body

43. Effects of Radiation on Various Cell Types
Blood Cells
Whole body dose of 25 rad (0.25 Gy) produces hematologic depression within a few days
Most blood cells are manufactured in the bone marrow
Radiation causes a decrease in the production of immature blood cells (stem, or precursor cells)
This produces a decrease in the number of mature cells in the bloodstream
The higher the dose, the greater the severity of cell depletion

44. Radiation and Blood Cells
Lymphocytes
White blood cells
Live for about 24 hours
25 rads will depress the number of these cells in circulating blood
These are the most sensitive cells in the human body

45. Epithelial Tissue Lines and covers body tissue
These cells lie close together
Contains no blood vessels
Regenerates through mitosis
Found in the lining of intestines, mucous lining of respiratory tract, pulmonary alveoli, and lining of blood and lymphatic vessels
It is constantly regenerated by the body and is very radiosensitive

46. Muscle Tissue Contains fibers that affect organ, or body movement
Highly specialized, non-dividing tissue
Insensitive to radiation

47. Nervous Tissue Conductive tissue – found in the brain and spinal cord
Nerve cells are highly specialized in the adult and do not divide
A single exposure of 5000 rads may lead to death within hours or days
Developing nerve cells are highly radiosensitive in the fetus
Irradiation of the fetus can lead to congenital anomalies

48. Reproductive Cells These cells are relatively radiosensitive
Radiosensitivity depends on cell maturity
A radiation dose of 200 rad can cause temporary sterility for about a year in the male
500 – 600 rads can cause permanent sterility
10 rads can depress the sperm count

49. Reproductive Cells
Few diagnostic therapy come close to delivering a dose of 10 rads
In the female, ova do not divide constantly
Temporary sterility occurs from a dose of 200 rads to the ovaries
500 rads can cause permanent sterility
10 rads may produce menstrual irregularities

50. Dose-response Relationship Curves
Linear-nonthreshold curve estimates the risk of associated with low-level radiation
Leukemia, breast cancer, and heritable damage are presumed to follow this curve
Leukemia occurrences in Hiroshima and Nagasaki support the use of this curve
This curve somewhat exaggerates the seriousness of effects at low-level radiation
It accurately reflects the effects of high-LET radiation at higher doses

51. Dose-response Relationship Curves
Linear-threshold curve
Used for nonstochastic effects such as skin erythema and hematologic depression
Non-linear-threshold curve
Used to determine high dose response in radiation therapy
Indicates the existence of a threshold

52. Threshold Curves

53. Threshold Curves

54. The Factors that Determine Somatic and Genetic Damage
The quantity of ionizing radiation received
The ability of the ionizing radiation to cause ionization of human tissue
The amount of body area exposed
The specific body parts exposed
The greatest amount of biologic damage is produced by a large dose of high-LET delivered to a large or radiosensitivity area of the body