Chapter 34 Principles of Radiobiology

1. Chapter 34 Principles of Radiobiology • In 1906, two French scientists, Bergonie and Tribondeau, theorized and observed that radiosensitivity was a function of the metabolic state of the tissue being irradiated. There observations became the • Law of Bergonie & Tribondeau

2. Law of Bergonie & Tribondeau • Stem cells are radiosensitive; mature cells are radio-resistant. • Younger tissues and organs are radiosensitive. • Tissues with high metabolic activity are radiosenstive. • High proliferation rate for cells and high growth rate for tissues result in increased radiosensitivity.

3. Law of Bergonie & Tribondeau • Basically it states that radiosensitivity of living tissue varies with maturity and metabolism. • In diagnostic imaging the law serves to remind us that a fetus is considerably more sensitive to radiation exposure than a child or mature adult.

4. Physical factors Affecting Radiosensitivity • When tissue is irradiated, the response of the tissue is determined principally by the amount of energy deposited per unit of mass: the dose in Rads (Gy). • Even under controlled conditions, the response to like exposure may be different.

5. Physical factors Affecting Radiosensitivity • Physical property factors • Linear energy transfer (LET) • Relative Biological Effectiveness (RBE) • Fractionation and Protraction

6. Linear Energy Transfer • The rate which energy is transferred from ionization to soft tissue is the (LET). • It is another method of expressing radiation quality and determining the value of the tissue weight factor used in radiation protection. • It is expressed in the units of kiloelectron volts of energy transferred per micrometer in soft tissue.

7. Linear Energy Transfer • The ability of ionizing radiation to produce a biologic response increases as the LET of the radiation increases. • The LET of diagnostic x-rays is approximately 3 keV/µm.

8. Relative Biologic Effectiveness • As the LET of the radiation increases, the ability to produce biologic damage also increases. This quantification is referred to as the Relative Biologic Effects (RBE). • The RBE of diagnostic x-ray is 1. • Radiations with a lower LET will have a RBE of less than 1. • Radiations with a higher LET will have a RBE greater than 1.

9. The LET & RBE of Various Radiations

10. LET & RBE Graph • As the LET increases, the RBE also increases but a maximum level is reached followed by a reduction due to overkill.

11. Fractionation & Protraction • If the dose is administered over a long time rather than quickly, the effects of that dose will be less. • If the time of irradiation is lengthened, a higher dose is required to produce the same effect. • Dose protraction and fractionation cause less effect allowing time for intracellular repair and tissue recovery.

12. Protraction • If we give an exposure of 600 rads at 300 rads/minute, the effects will be less than if the same exposure is given at 600 rads/ minute. This us called protraction.

13. Fractionation • If that 600 rads is given at 150 rad per day over 4 days, the effects would be less than 600 rads given over 1 day. • This is called fractionation.

14. Biologic Factors Affecting Radiosensitity • Oxygen Effect: Tissue is more sensitive to radiation if the tissue is oxygenated or aerobic state than when irradiated in the anoxic ( w/o oxygen) or hypoxic state (low oxygen) state. • The characteristic of tissue is described numerically as the Oxygen Enhancement Ratio. (OER)

15. Biologic Factors Affecting Radiosensitity • Oxygen Enhancement Effect for diagnostic x-ray is full oxygenation. • The OER is LET dependent. The OER for highest for low LET radiation having a maximum value of approximately 3, decreasing to 1 for high LET radiation.

16. Oxygen Enhancement Ratio • The OER is high for low LET radiation and decreases as the LET increases.

17. Biologic Factors Affecting Radiosensitity • Age affects the biologic structure’s radiosensitivity. Humans are most sensitive before birth. • Sensitivity decreases until maturity. • In old age, sensitivity increases again.

18. Biologic Factors Affecting Radiosensitity Recovery: If the dose of radiation is sufficient to kill the cell before its next division, interphase death will occur. • If the dose is sub lethal, the cell may recover from the damage. • Some cell types are more capable of recovery.

19. Biologic Factors Affecting Radiosensitity • Recovery: At the whole body level, recovery is assisted by repopulation by the surviving cells. • If the tissue or organ receives a sufficient dose, it will respond by shrinking in size. This is called atrophy. • Atrophy happens because cells die, disintegrate and are carried away as waste.

20. Recovery • Recovery = Intracellular Repair+ Repopulation • Some chemical agents can modify radiation response. • Radiosensitizers enhance the effects • Radioprotectors reduce the effects

21. Radiosensitizers • Agents that enhance the effects of radiation are radiosensitizers. Example include: • Halogenated pyrimidines that become incorporated in the cell DNA and effectively double the effect of the radiation. • Vitamin K • Must be present at the time of irradiation.

22. Radioprotectors • Radio protector agents exist but have not found any human application. They must be given in toxic levels to be effective. • The protective agent can be worse than the radiation.

23. Hormesis • There is a growing body of radiobiologic evidence that suggest that a little bit of radiation is good for you. • Studies have shown that animals live longer lives when they receive low radiation doses.

24. Hormesis • The prevailing explanation is that a little radiation stimulates hormonal and immune responses to toxic environmental agents. • Regardless of Hormesis, we still practice ALARA as a known safe response to radiation safety.

25. Radiation Dose-Response Relationships • Radiobiology is a relatively new science. Interest increased in the 1940’s with the advent of the atomic age. • The object of nearly all of the research is the establishment of radiation dose-response relationships.

26. Radiation Dose-Response Relationships • Radiation Dose-Response Relationships have two important functions. • Designing therapeutic treatment routines for patients with cancer. • Provide information on the effects of low dose irradiation.

27. Radiation Dose Response Relationship Characteristics • Every exposure has two characteristics. It is either: • Linear • Threshold or • Non-Threshold • Non-Linear • Threshold or • Non-Threshold

28. Linear Dose-Response Relationship • Radiation-induced cancer and genetic effects follow a linear, nonthreshold dose response relationship. • Any exposure above zero is expected to cause some response. • Exposure can also be a linear threshold type where the dose axis is greater than zero.

29. Linear Dose-Response Relationship • Linear dose graphs have a straight line graph starting at zero for nonthreshold exposures or at a point greater than zero for threshold exposures.

30. Non-Linear Dose Response • All other radiation dose response relationships are defined as non-linear. • If the dose response curve starts at zero, it has a nonthreshold. • The shape of the curve will determine the rate of response.

31. Non-Linear Dose Response • Radiation death and skin effects of high dose fluoroscopy follow a sigmoid-type dose relationship. • At exposure levels below where the graph threshold, no effect had been identified. • The point where the curve stops bending up is the inflection point.

32. Non-linear Dose Response • Above the inflection point, the incremental dose increase becomes less effective. • Dose response graphs are used to discuss the type and degree of radiation injury.

33. Non-Linear Dose Response • In diagnostic exposures it is most exclusively concerned with late effects and therefore with linear non-threshold dose response relationships. • The principle interest in diagnostic responses to very low level exposures.

34. Linear Non-threshold Dose Response • Since this cannot be done directly, the dose response is extrapolated from known high dose exposures using the linear response graphs.

35. Exposure to Diagnostic X-ray • Diagnostic x-ray is usually and primarily concerned with the late effects of radiation exposure. • The existence of radiation hormesis is highly controversial. Regardless of it’s existence, no human response has been observed following doses less than 10 rad (100 mGy).

36. Chapter 35 Molecular & Cellular Radiobiology • When macromolecules are irradiated in vitro( outside the body) it take a considerable amount of radiation to produce a measurable effect. • Irradiation in vivo (inside the body) in a living cell in solution, macromolecules are considerably more radiosensitive in their natural state.

37. Results of irradiation of macro-molecules. • There are three major results of irradiation of macro-molecules in solution: • A-Main chain Scission • B- Cross linking • C- Point lesions

38. Main Chain Scission • Main-chain scission is the breakage of the backbone of the long chain macro-molecules. • This results in many smaller molecules which still may be macro-molecules.

39. Main Chain Scission • This not only changes the size of the molecule but the viscosity of the solution also increases. • Measurement of the viscosity determines the degree of main chain scission.

40. Cross Linking • B- Cross Linking • Some macro-molecules have small spur like side structures extending off the main chain. • Other produce the spurs as a result of irradiation.

41. Cross Linking • These structures can behave as though they had a sticky substance on end. • They can attach to other macro-molecules or another segment of the same molecule. • Also increases viscosity of the solution.

42. Point Lesions • Radiation interaction can also result in disruption of a single chemical bond. • Such point lesions are not detectable but can result in minor modifications to the cell that can cause it to malfunction.

43. Point Lesions • Radiation interaction can also result in disruption of a single chemical bond. • Such point lesions are not detectable but can result in minor modifications to the cell that can cause it to malfunction.

44. Point Lesions • At low radiation doses, point lesions are considered to be the cellular radiation damage resulting in the late effects observed at the whole body level.

45. Irradiation of Macro-molecules • Laboratory experiments have shown that all these types of radiation effects on macro-molecules are reversible through intracellular repair and recovery. • Radiation damage may result in cell death or late effects. • DNA is the most radiosensitive molecule. It forms chromosomes and controls cell and human growth and development.

46. Normal & Radiation Damaged Chromosomes • Normal • Terminal deletion • Dicentrics Formation • Ring formation

47. Radiation Responses of DNA • Types of damage. • One side rail severed. • Both side rails severed • Cross linking • Rung breakage All are reversible

48. Point mutation • A change or a loss of a base is called a point mutation. • It destroys the triplet code and may not be reversible. • It is a molecular lesion of the DNA. • One of the daughter cells will receive incorrect genetic code.

49. Principle effects of DNA irradiation • The principle effects are: • Cell death • Malignant disease • Genetic damage • The latter two conform to the linear, nonthreshold dose response relationship.

50. Radiolysis of Water • Because the human body is an aqueous solution containing 80% water molecules, irradiation of water represents the principle radiation interaction with the body. • When water is irradiated, it dissociates into other molecular products. This is referred to as radiolysis of water.