1. 1 RAD PROT PT 2 Radiobiology and Cells WEEK 7 – 9 RT 244 (2006 – 2010) RADIOBIOLOGY Radiation Protection & Biology CD SERIES 2 - 6 RADIATION PROTECTION AND EFFECTS

2. 2 CD # 2 - CELLULAR RADIATION + STAT CH 4, 5 & 6 What type of Radiation Response is this? How much rads does it take to see this?

3. 3 # 2 – CELLS MADE OF PROTOPLASM RESPONSIBLE FOR THE METABOLISM OF THE CELLS COMPOSED MOSTLY OF WATER (80-85%) CD 2 - # 2

4. 4 A quick review of interactions Stat Ch 1 & 2

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8. 8 PHOTOELECTRIC ABSORBTION IS WHAT GIVES US THE CONTRAST ON THE FILM

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12. 12 DNA IN THE NUCLEUS CONTAINS THE GENETIC MATERIAL CONTROLS CELL DIVISION + MULITPLICATION AND BIOCHEMICAL REACTIONS THAT OCCUR IN THE LIVING CELL

13. 13 6 – DNA IS THE ESSENTIAL INGREDIENT IN THE 46 HUMAN CHROMOSOMES DNA CARRIES THE GENETIC CODE FOR CELL REPRODUCTION AND CELL ACTIVITY DNA EXISTS MOSTLY IN THE NUCLEUS OF THE CELL RADIATION INDUCED CHROMOSOME DAMAGE IS ONE OF THE MOST IMPORTANT REASONS FOR LIMITING RADIATION EXPOSURE.

14. 14 Repair Enzymes SOME CHROMOSOME DAMAGE CAN BE REVERSED BY REPAIR ENZYMES - ( 5 RADS) IF REPAIR IS NOT POSSIBLE – CELL DEATH OCCURS TOO MANY CELLS DIE – TISSUE OR ORGAN DAMAGE OCCURS (Rad Therapy – therapeutic ratio (p 66)

15. 15 WHEN DNA DAMAGE RESULTS IN ABNORMAL METABOLIC ACTIVITY – THERE CAN BE UNCONTROLLED CELL GROWTH – THIS IS WHAT OCCURS IN RADIATION INDUCED MALIGNANT DISEASE. WHEN DNA DAMAGE OCCURS THE EFFECTS MAY NOT SHOW UP UNTIL FUTURE GENERATIONS

16. 16 CD 2 - # 6

17. 17 CD2 # 21 21- CELL DAMAGE FROM RADIATION

18. 18 23 – Cell Division How and why radiation effects the human body HITS NUCLEUS – DAMAGE TO DNA HITS WATER – RADIOLYSIS OCCURS – CAN SET OFF A REACTION RESULTING IN CELL DEATH A BREAK IN THE CELL MEMBRANE CAN EXPOSE THE CELL TO OUTSIDE ELEMENTS

19. 19 CELL DIVISION (#24) Multiplication process where cells divide MITOSIS SOMATIC CELLS EVERY CELL THAT IS NOT GENETIC MEIOSIS REPRODUCTIVE CELLS GERM CELLS sperm + eggs

20. 20 4 PHASES OF MITOSIS INTERPHASE – THE PROCESS BEFORE MITOSIS BEGINS PROPHASE – nucleus swells – DNA takes structure METAPHASE – MOST SENSITIVE STAGE FOR DAMAGE –Chromosomes line up in the center ANAPHASE TELOPHASE –cells split to daughter cells

21. 21 METAPHASE DURING THIS PHASE CELL DIVISION CAN BE STOPPED AND EVALUATED CHROMOSOME DAMAGE CAUSED BY RADIATION DAMAGE CAN BE SEEN

22. 22 CD2 - #28 CELL DIVISION

23. 23 CELL DIVISION FROM 1 2 4 8 16 32 64 128 256 512 1024 “never ending”

24. 24 # 32 MEIOSIS – THE SPERM AND OVUM 46 Chromosone reduced to 23 for Females + 23 for Males to unite during reproduction

25. 25 CD 2 - # 34 34 * CELLULAR EFFECTS OF RADIATION Vulnerability of all cells to Radiation

26. 26 CD 2 - # 36 36 CELL THEORY – TARGET THEORY – MASTER MOLECULE (DNA Molecule) If this is destroyed the cell can die (Direct or Indirect hit)

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28. 28 CD 2 - # 37 MASTER MOLECULE

29. 29 CD 2 # 37

30. 30 CELL DEATH - MASTER MOLECULE USUALLY DNA HIT

31. 31 CD 2 # 35

32. 32 Radiolysis poison water theory H 2 O molecules - Ejection of electron = free radical H2 O 2 = hydrogen peroxide

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34. 34 LET linear energy transfer The amount of energy that may be deposited in tissue as radiation passes Factor in assessing potential damage to organs/tissues from exposure to ionizing radiation ↑ ENERGY = ↓ LET - passes through

35. 35 Damage from LET High – LET (alpha particles – radon) Internal contamination implanted, ingested or inhaled Potiental for irreparable damge

36. 36 RBE ↑ WITH O 2 Relative Biologic Effectiveness Describes the capabilities of radiation with differing LET’s to produce a particular biologic reaction Weighting factor (EqD) equivalent dose

37. 37 TYPES OF RADIATON (ALL CAUSE IONIZATION) PARTICULATE (HIGH LET) ALPHA BETA FAST NEUTRONS More destructive ELECTROMAGNETIC (LOW LET) XRAY GAMMA (damaged caused by indirect action = free radicals – can be repaired)

38. 38 Quality (Weighting) Factor How dangerous the type of radiation is Alpha + fast neutrons = 20 X-ray, Beta, Gamma = 1 (why “fluffy” died!)

39. 39 OER Oxygen Enhancement Ratio OXYGEN IN CELL INCREASES LET PT IN HYPERBARIC TREATMENT AND ON OXYGEN LET IS AFFECTED BY OXYGEN

40. 40 CD 2 - # 38

41. 41 # 39 – RADIAITON DAMAGE TO DNA EFFECTS OF RADIATION DAMAGE DNA – LOSS OF CONTROL OVER CELL FUNCTION PRODUCTION OF DAUGHTER CELLS WITH GREATER LOSS OF CELL FUNCTION Inablity to divide or reproduce OTHER CELL COMPONENTS LOSS OF IMPORTANT CELL FUNCTIONS PRODUCTION OF TOXIC WASTES CELL DEATH

42. 42 #40 RADIATION DAMAGE TO CELL’S NUCLEUS –INSTANT DEATH –REPRODUCTIVE DEATH –APOPTOSIS- PROGRAMMED CELL DEATH –MITOTIC, OR GENETIC DEATH OR DELAY –INTERFERENCE OF FUNCTION –CHROMOSOME BREAKAGE

43. 43 INSTANT DEATH – 1000 GY (100,000 RAD) REPRODUCTIVE DEATH - 1 – 10 GY ( 100 – 1000) APOPTOSIS – CELL DEATH BEFORE DIVISION MITOTIC/ GENETIC DEATH – CELL’S DEATH AFTER DIVISION OR DELAY – JUST BEFORE CELL DIVISION INTERFERENCE OF FUNCTION MAY BE REPARIED BY ENZYMES OR PERMANENTYLY DAMAGE CELL FUNCTION CHROMOSOME BREAKAGE – CAUSE GENETIC MUTATIONS IN FUTURE GENERATIONS

44. 44 Stages of Radiation Damage

45. 45 # 43 – IONIZING RADIATION CAN PERMANENTLY DAMAGE CELL FUNCTIONS TEMPORARILY INTERFERE WITH CELL FUNCTIONS CAUSE CHROMSOME BREAKAGE CAUSE GENEITC DAMAGE IN FUTURE GENERATIONS

46. 46 ALL CELLS ARE NOT EQUAL # 44 – CELL RADIOSENSITIVITY SOME CELLS ARE MORE: SENSITIVE TO DAMAGE MORE EAISLY REPAIRED MORE QUICKLY REPLACED All of these factors affect the radiosensitivity of the cell

47. 47 The Law of Bergonie & Tribondeaux Cells that are most sensitive to radiation Young – immature cells Stem Cells Highly dividing (mitotic) cells CD 2 #45

48. 48 Radiosensitivy Is Related To Cell Function, Cell Maturity And Cell Division Rate Conversely – Cells Least Sensitive Are: Cells That Reproduce Slowly Short Mitotic Cycle Least Degree Of Specialization Most Mature

49. 49 CELLS MOST SENSITIVE WHITE BLOOD CELLS – LYMPHOCYTES RED BLOOD CELLS – ERYTHOROCYTES BASAL CELLS OF THE SKIN INTESTINAL CELLS DEVELOPING NERVE CELLS OF EMBRYO IMMATURE REPRODUCTIVE CELLS EPITHELIAL CELLS THAT LINE BLOOD LYMPHATIC VESSELLS (80% BODY) CELLS THAT REPRODUCE THE MOST – SPEND THE MOST TIME IN THEIR REPRODUCTIVE STATE

50. 50 LYMPHOCYTE PG.103 SUBGROUP OF WBC ONLY LIVE FOR 24 HOURS ARE MANUFACTURED IN BONE MARROW MOST RADIOSENSITIVE BLOOD CELL 25 RADS CAN DEPRESS # OF CELLS LESS ABILITY TO FIGHT INFECTIONS

51. 51 RADIOINSENSTIVE MATURE BONE CELLS MATURE NERVE CELLS MUSCLE CELLS MATURE REPRODUCTIVE CELLS MATURE RED BLOOD CELLS SCAR TISSUE CELLS

52. 52 CD 2 - # 48

53. 53 RHB – SYLLABUS PG 47 MOST – LEAST SENSITIVE LYMPHOCYTES (WBC) ETHROCYTES (RBC) EPITHELIAL CELLS (SKIN) ENDOTHELIAL CELLS (LINE BLOOD VESSELS CONNECTIVE TISSUE CELLS BONE CELLS MUSCLE CELLS NERVE CELLS BRAIN CELLS

54. 54 Muscles & Nerve Cells HIGHLY SPECIALIZED DO NOT DIVIDE SO ARE REALTIVELY INSENSITIVE TO RADIATION

55. 55 GERM CELLS in males HIGHLY RADIOSENSITIVE = DEPENDS OF STAGE OF DEVELOPMENT MATURE SPERM – LESS SENSITIVE UNDEVELOPED – VERY SENSITIVE 200 RADS CAN CAUSE TEMP STERILITY FOR 12 MONTHS (500- 600 permanent) 10 rads – possible genetic mutations (future generations) wait a few months

56. 56 GERM CELLS in Females (present at birth) HIGHLY RADIOSENSITIVE = DEPENDS OF STAGE OF DEVELOPMENT Mature ovum do not divide frequently (20-30 yrs old - least sensitive) Immature very sensitive If exposed ova meets sperm – may contain damaged chromosomes – passing genetic damage to offspring = CONGENTIAL ABNORMALITIES

57. 57 RADIATION DAMAGE CHROMOSOME ABBERATION SEEN WITH HLC – FLUOROSCOPY LONG STUDIES (CARDIAC CATH)

58. 58 RAD PROTECTION & RADIOBIOLOGY CD’S 3 4 5 6 NOT YET ON POWERPOINT In class highlights of CH 4/5/6 Stat Nice to know vs Need to know!

59. 59 The use of higher kilovoltage (kVp) and lower milliamperage and exposure time in seconds (mAs) reduces patient dose. A, The use of high kVp and low mAs results in a high-energy, penetrating x-ray beam and a small patient absorbed dose. B, The use of low kVp and high mAs results in a low-energy x-ray beam, most of which is easily absorbed by the patient. C, Example of a higher-kVp, lower mAs technique resulting in a 70% reduction in patient exposure without significantly compromising radiographic quality

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63. 63 TISSUE SENSITIVITY - review Most Sensitive: ? Least sensitive:?

64. 64 TISSUE SENSITIVITY - review Most Sensitive: Blood-forming organs Reproductive organs Skin Least sensitive: Bone and teeth Muscle Nervous system

65. 65 RadiosensitiveRadioresistant Breast tissueHeart tissue Bone marrow cellsLarge arteries Mucosa lining of small intestines Large veins Sebaceous (fat) glands of skinMature blood cells Immune response cellsNeurons All stem cell populationsMuscle cells Lymphocytes

66. 66 Summary of Tissue Sensitivity