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RADIATION PROTECTION IN DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY

IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology. RADIATION PROTECTION IN DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY. L 3: Biological effects of ionizing radiation. Introduction. Subject matter: radiobiology

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RADIATION PROTECTION IN DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY

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  1. IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology RADIATION PROTECTION INDIAGNOSTIC ANDINTERVENTIONAL RADIOLOGY L 3: Biological effects of ionizing radiation

  2. Introduction • Subject matter: radiobiology • The mechanisms of different types of biological effects following exposure to ionizing radiation • Types of models used to derive risk coefficients for estimating the detriment 3 : Biological effects of ionizing radiation

  3. Topics • Classification of radiation health effects • Factors affecting radio sensitivity • Dose-effect response curve • Whole body response: acute radiation syndrome • Effects of antenatal exposure and delayed effects of radiation • Epidemiology 3 : Biological effects of ionizing radiation

  4. Overview • To become familiar with the mechanisms of different types of biological effects following exposure to ionizing radiation. To be aware of the models used to derive risk coefficients for estimating the detriment. 3 : Biological effects of ionizing radiation

  5. IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology Part 3: Biological effect of ionizing radiation Topic 1: Classification of radiation health effects

  6. Radiation health effects TYPE OF EFFECTS CELL TRANSFORMATION CELL DEATH BOTH ANTENATAL somatic and hereditary expressed in the foetus, in the live born or descendants STOCHASTIC somatic & hereditary epidemiologically attributable in large populations DETERMINISTIC Somatic Clinically attributable in the exposed individual 3 : Biological effects of ionizing radiation

  7. Biological effects of ionizing radiation • Deterministic • e.g. Lens opacities, skin injuries, • infertility, epilation, etc • Stochastic • Cancer, genetic effects. 3 : Biological effects of ionizing radiation

  8. Deterministic effects • Deterministic (Threshold or non-stochastic) • Existence of a dose threshold value (below this dose, the effect is not observable) • Severity of the effect increases with dose • A large number of cells are involved Radiation injury from an industrial source 3 : Biological effects of ionizing radiation

  9. Threshold Doses for Deterministic Effects • Cataracts of the lens of the eye 2-10 Gy • Permanent sterility • males 3.5-6 Gy • females 2.5-6 Gy • Temporary sterility • males 0.15 Gy • females 0.6 Gy Severity of effect dose threshold 3 : Biological effects of ionizing radiation

  10. Stochastic Effects • Stochastic(Non-Threshold) • No threshold • Probability of the effect increases with dose • Generally occurs with a single cell e.g., cancer, genetic effects 3 : Biological effects of ionizing radiation

  11. No change DNA mutation radiation hit cell nucleus!

  12. DIRECT ACTION INDIRECT ACTION

  13. Viable Cell Mutation repaired Unviable Cell Cell death Cancer ? DNA Mutation Cell survives but mutated

  14. Outcomes after cell exposure DAMAGE TO DNA TRANSFORMED CELL CELL DEATH (APOPTOSIS) DAMAGE REPAIRED 3 : Biological effects of ionizing radiation

  15. Outcomes after cell exposure DAMAGE TO DNA DAMAGE REPAIRED CELL NECROSIS OR APOPTOSIS TRANSFORMED CELL 3 : Biological effects of ionizing radiation

  16. How DNA is repaired ?

  17. Altered base Enzyme Glycosylases recognizes lesion and releases damaged base AP-endunuclease makes incision and releases remaining sugar DNA-polymerase fillsresulting gap but nick remains DNA ligase seals the nick Repair completed DNA has been repaired with no loss of genetic information

  18. Repair of DNA damage • RADIOBIOLOGISTS ASSUME THAT THE REPAIR SYSTEM IS NOT 100% EFFECTIVE. 3 : Biological effects of ionizing radiation

  19. Response Conditioning dose Response Challenging dose ADAPTIVE RESPONSE Response Challenging dose Conditioning dose

  20. Outcomes after cell exposure DAMAGE TO DNA CELL NECROSIS OR APOPTOSIS DAMAGE REPAIRED TRANSFORMED CELL 3 : Biological effects of ionizing radiation

  21. Normal human lymphocyte: chromosomes uniformly distributed

  22. Apoptotic cell: chromosomes and nucleus fragmented and collapsed into apoptotic bodies

  23. Effects of cell death Probability of cell death 100% Acute dose (in mSv) 5000 3 : Biological effects of ionizing radiation

  24. Outcomes after cell exposure DAMAGE TO DNA CELL NECROSIS OR APOPTOSIS DAMAGE REPAIRED TRANSFORMED CELL 3 : Biological effects of ionizing radiation

  25. Chromosomal deletions 3 : Biological effects of ionizing radiation

  26. Chromosomal translocations 3 : Biological effects of ionizing radiation

  27. CANCER INITIATION TUMOR PROMOTION MALIGNANT PROGRESSION STEAM CELL NECROSIS OR APOPTOSIS MUTATION MALIGNANT TRANSFOMATION METASTASIS DIVISION

  28. NORMAL TISSUE

  29. CELL INITIATION An initiating event creates a mutation in one of the basal cells

  30. DYSPLASIA More mutations occurred. The initiated cell has gained proliferative advantages. Rapidly dividing cells begin to accumulate within the epithelium.

  31. BENIGN TUMOR More changes within the proliferative cell line lead to full tumor development.

  32. MALIGNANT TUMOR The tumor breaks trough the basal lamina. The cells are irregularly shaped and the cell line is immortal. They have an increased mobility and invasiveness.

  33. METASTASIS Cancer cells break through the wall of a lymphatic vessel or blood capillary. They can now migrate throughout the body and potentially seed new tumors.

  34. A simple generalized scheme for multistage oncogenesis Damage to chromosomal DNA of a normal target cell Failure to correct DNA repair Appearance of specific neoplasia-initiating mutation Promotional growth of pre-neoplasm Conversion to overtly malignant phenotype Malignant progression and tumour spread

  35. -15 Energy deposition 10 PHYSICAL INTERACTIONS Excitation/ionization -12 Initial particle tracks 10 Radical formation -9 10 PHYSICO-CHEMICAL INTERACTIONS Diffusion, chemical reactions Initial DNA damage -6 10 ) c e s ( -3 DNA breaks / base damage E 1 ms 10 M I T 0 1 second 10 Repair processes Timing of events leading to radiation effects. Damage fixation BIOLOGICAL RESPONSE 3 10 Cell killing 1 hour Mutations/transformations/aberrations 1 day 6 10 Proliferation of "damaged" cells Promotion/completion 1 year Teratogenesis MEDICAL EFFECTS 9 10 Cancer 100 years Hereditary defects

  36. IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology Part 3: Biological effect of ionizing radiation Topic 2: Factors affecting the radiosensitivity

  37. Radiosensitivity [RS] (1) • RS = Probability of a cell, tissue or organ of suffering an effect per unit of dose. • Bergonie and Tribondeau (1906): “RS LAWS”: RS will be greater if the cell: • Is highly mitotic. • Is undifferentiated. • Has a high cariocinetic future. 3 : Biological effects of ionizing radiation

  38. Radiosensitivity (2) High RS Medium RS Low RS Bone Marrow Spleen Thymus Lymphatic nodes Gonads Eye lens Lymphocytes (exception to the RS laws) Skin Mesoderm organs (liver, heart, lungs…) Muscle Bones Nervous system 3 : Biological effects of ionizing radiation

  39. Factors affecting the radiosensitivity • Physical • LET (linear energy transfer):  RS • Dose rate:  RS • Chemical • Increase RS: OXYGEN, cytotoxic drugs. • Decrease RS: SULFURE (cys, cysteamine…) • Biological • Cycle status: •  RS: G2, M •  RS: S • Repair of damage (sub-lethal damage may be repaired e.g. fractionated dose) % survivor cells  LET  LET G0 M M M G2 G1 S 3 : Biological effects of ionizing radiation

  40. IAEA Training Material on Radiation Protection in Diagnostic and Interventional Radiology Part 3: Biological effect of ionizing radiation Topic 3: Dose-effect response curve

  41. Systemic effects • Effects may be morphological and/or functional • Factors: • Which Organ • How much Dose • Effects • Immediate (usually reversible): < 6 months e.g.: inflammation, bleeding. • Delayed (usually irreversible): > 6 months e.g.: atrophy, sclerosis, fibrosis. • Categorization of dose • < 1 Gy: LOW DOSE • 1-10 Gy: MODERATE DOSE • > 10 Gy: HIGH DOSE • Regeneration means replacement by the original tissue while Repair means replacement by connective tissue. 3 : Biological effects of ionizing radiation

  42. EPIDERMIS DERMIS Skin effects • Following the RS laws (Bergonie and Tribondeau), the most RS cells are those from the basal stratum of the epidermis. • Effects are: • Erythema: 1 to 24 hours after irradiation of about 3-5 Gy • Alopecia(*): 5 Gy is reversible; 20 Gy is irreversible. • Pigmentation: Reversible, appears 8 days after irradiation. • Dry or moist desquamation: traduces epidermal hypoplasia (dose  20 Gy). • Delayed effects: teleangiectasia (**), fibrosis. Histologic view of the skin From “Atlas de Histologia...”. J. Boya Basal stratum cells, highly mitotic, some of them with melanin, responsible of pigmentation. (*):alopecia: loss or absence of hair (**): ectasia: swelling of part of the body 3 : Biological effects of ionizing radiation

  43. Skin reactions Threshold Weeks to Injury Dose to Onset Skin (Sv) Early transient erythema 2 <<1 Temporary epilation 3 3 Main erythema 6 1.5 Permanent epilation 7 3 Skin damage from prolonged fluoroscopic exposure Dry desquamation 10 4 Invasive fibrosis 10 Dermal atrophy 11 >14 Telangiectasis 12 >52 Moist desquamation 15 4 Late erythema 15 6-10 Dermal necrosis 18 >10 Secondary ulceration 20 >6 3 : Biological effects of ionizing radiation

  44. Skin injuries 3 : Biological effects of ionizing radiation

  45. Skin injuries 3 : Biological effects of ionizing radiation

  46. Effects in eye • Eye lens is highly RS. • Coagulation of proteins occur with doses greater than 2 Gy. • There are 2 basic effects: Histologic view of eye: Effect Sv single brief exposure Sv/year for many years Detectable opacities 0.5-2.0 > 0.1 From “Atlas de Histologia...”. J. Boya Eye lens is highly RS, moreover, it is surrounded by highly RS cuboid cells. Visual impairment (cataract) 5.0 > 0.15 3 : Biological effects of ionizing radiation

  47. Eye injuries 3 : Biological effects of ionizing radiation

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