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
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
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
24
# 32 MEIOSIS – THE SPERM AND OVUM
• 46 Chromosone reduced to
• 23 for Females +• 23 for Males • to unite during
reproduction
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)
32 Radiolysispoison water theory
• H 2 O molecules -
• Ejection of electron = free radical
• H2 O 2 = hydrogen peroxide
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 O2
Relative Biologic Effectiveness
• Describes the capabilities of radiation with differing LET’s to produce a particular biologic reaction
• Weighting factor
• (EqD) 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
41
# 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
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
• 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
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
53
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
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 (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
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