1 RAD PROT PT 2 Radiobiology and Cells

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

4 A quick review of interactions Stat Ch 1 & 2

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

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

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 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 • 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 CD 2 - # 6

17 CD 2 # 21 21 - CELL DAMAGE FROM RADIATION

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

22 CD 2 - #28 CELL DIVISION

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

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

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

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 CD 2 - # 37 MASTER MOLECULE

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30 CELL DEATH MASTER MOLECULE USUALLY DNA HIT

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

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

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 • (Eq. D) equivalent dose

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

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

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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 #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 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 Stages of Radiation Damage

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

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 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 • 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 CELLS MOST SENSITIVE CELLS THAT REPRODUCE THE MOST – SPEND THE MOST TIME IN THEIR REPRODUCTIVE STATE • • 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)

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 RADIOINSENSTIVE • • • MATURE BONE CELLS MATURE NERVE CELLS MUSCLE CELLS MATURE REPRODUCTIVE CELLS MATURE RED BLOOD CELLS SCAR TISSUE CELLS

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

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

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

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

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

65 Radiosensitive Radioresistant Breast tissue Heart tissue Bone marrow cells Large arteries Mucosa lining of small intestines Large veins Sebaceous (fat) glands of skin Mature blood cells Immune response cells Neurons All stem cell populations Muscle cells Lymphocytes

66 Summary of Tissue Sensitivity