1RAD PROT

PT 2Radiobiology

and CellsWEEK 7 – 9 RT 244 (2006 – 2010)

RADIOBIOLOGYRadiation Protection & BiologyCD 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

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A quick review of interactionsStat Ch 1 & 2

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6

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• PHOTOELECTRIC

ABSORBTION

IS WHAT GIVES US

THE CONTRAST

ON THE FILM

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XXXXX

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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.

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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)

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• 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

16CD 2 - # 6

17CD2 # 21

21- CELL DAMAGE FROM RADIATION

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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

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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

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METAPHASE

• DURING THIS PHASE

• CELL DIVISION CAN BE STOPPED AND EVALUATED

• CHROMOSOME DAMAGE CAUSED BY RADIATION DAMAGE CAN BE SEEN

22CD2 - #28

CELL DIVISION

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CELL DIVISION FROM

• 1 • 2 • 4• 8• 16

• 32• 64• 128• 256• 512• 1024• “never ending”

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# 32 MEIOSIS – THE SPERM AND OVUM

• 46 Chromosone reduced to

• 23 for Females +• 23 for Males • to unite during

reproduction

25CD 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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28CD 2 - # 37 MASTER MOLECULE

29CD 2 # 37

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CELL DEATH -

MASTER MOLECULE

USUALLY DNA HIT

31CD 2 # 35

32 Radiolysispoison water theory

• H 2 O molecules -

• Ejection of electron = free radical

• H2 O 2 = hydrogen peroxide

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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

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Damage from LET

• High – LET (alpha particles – radon)

• Internal contamination

• implanted, ingested or inhaled

• Potiental for irreparable damge

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RBE ↑ WITH O2

Relative Biologic Effectiveness

• Describes the capabilities of radiation with differing LET’s to produce a particular biologic reaction

• Weighting factor

• (EqD) equivalent dose

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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)

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Quality (Weighting) Factor• How dangerous

the type of radiation is

• Alpha + fast neutrons = 20

• X-ray, Beta, Gamma = 1

• (why “fluffy” died!)

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OER Oxygen Enhancement Ratio

• OXYGEN IN CELL INCREASES LET

• PT IN HYPERBARIC TREATMENT AND ON OXYGEN

• LET IS AFFECTED BY OXYGEN

40 CD 2 - # 38

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# 39 – RADIAITON DAMAGE TO DNA

EFFECTS OF RADIATION DAMAGEDNA – LOSS OF CONTROL OVER CELL FUNCTIONPRODUCTION 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

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Stages of Radiation Damage

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# 43 – IONIZING RADIATION CAN

• PERMANENTLY DAMAGE CELL FUNCTIONS

• TEMPORARILY INTERFERE WITH CELL FUNCTIONS

• CAUSE CHROMSOME BREAKAGE

• CAUSE GENEITC DAMAGE IN FUTURE GENERATIONS

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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

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The Law of Bergonie & Tribondeaux

• Cells that are most sensitive to radiation

• Young – immature cells

• Stem Cells

• Highly dividing (mitotic) cells

CD 2 #45

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• 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

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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

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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

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RADIOINSENSTIVE

• MATURE BONE CELLS

• MATURE NERVE CELLS

• MUSCLE CELLS

• MATURE REPRODUCTIVE CELLS

• MATURE RED BLOOD CELLS

• SCAR TISSUE CELLS

52CD 2 - # 48

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RHB – SYLLABUS PG 47MOST – 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

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Muscles & Nerve Cells

• HIGHLY SPECIALIZED• DO NOT DIVIDE SO ARE REALTIVELY

INSENSITIVE TO RADIATION

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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

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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

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RADIATION DAMAGE

• CHROMOSOME ABBERATION SEEN

• WITH HLC – FLUOROSCOPY

• LONG STUDIES (CARDIAC CATH)

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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 (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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TISSUE SENSITIVITY - review

• Most Sensitive: ?

• Least sensitive:?

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TISSUE SENSITIVITY - review

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

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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  

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Summary of Tissue Sensitivity