Escolar Documentos
Profissional Documentos
Cultura Documentos
Module VIII-a
Historical background
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Discovery of X rays
(1895)
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Marie Curie
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Studies of Japanese
A-bomb survivors
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Excitation
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Ionization
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Mechananisms of damage
at molecular level
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Direct action
Ionizing radiation + RH
R - + H+
Bond breaks
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OH
O
I
II
R C = NH2
R C = NH
imidol (enol)
amide (ketol)
Tautomeric Shifts
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Indirect action
X ray
ray
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eP+
OHH+
Ho
OHo
- 10
Radiolysis of H2O
molecule
Shared electron
Shared electron
(free radicals)
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HO2
Ho
OHo
OHo
3nm
Ho
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Biochemical reactions
with ionizing radiation
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Single-strand breaks
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Mechanisms of DNA
repair
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Unrejoined DNA
double strand breaks
Cytotoxic effect
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Incorrect repair of
DNA damage
Mutations
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Chromosomes
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DNA SNGLE
STRAND BREAK
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DNA DOUBLE
STRAND BREAK
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Radiation induced
chromosomal aberrations
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Radiosensitivity of cell
in cell cycle
Relative
Survivability
G1
G2
G1
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Mitotic death
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NORMAL
IRRADIATED
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Interphase death
Why are peripheral blood lymphocytes highly
sensitive to radiation, although well differentiated?
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Radiation induced
membrane damage
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Modification of radiation
injury
Dose rate and fractionation
Radiation quality
Temperature
Chemical modification
Oxygen
Radiosensitizing agents
Radioprotective agents
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2.5
2.5
1.5
1.5
0.5
0.5
0
Acute
exposure
with high
dose rate
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Time
Prolonged exposure
with lower dose rate
Acute
dose Fractionated
dose
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Time
Radiation quality
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Dq
,037
1-1/e
1-1/e
D0
D0
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Temperature
For cell kiling effects, tissues are
more radiosensitive at higher
temperatures
Chromosome aberrations increase
at lower temperatures (suppression
of repair process)
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Chemical modification:
oxygen
Dissolved oxygen in tissues increases
stability and toxicity of free radicals
Oxygen enhancement ratio (OER) is
determined by:
OER =
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Radiosensitizing agents
Halogenated
and
substituted
analoges of DNA bases: 5-bromouracil and 6-thio-guanine
Electroaffinic compounds:
Nitroimidazoles
(misonidazole,
nitroimidazole, and nitrofuran)
sensitization
enhancement
ratio
(SER) of 1.2 to 1.4
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Radioprotective
agents
Thiols (cysteine, 2-mercaptoethylamine,
cystamine and thiourea). Thiols have dose
reduction factor (DRF) ratio of 1.4 to 2.0
They are thought to protect cells by
scavenging free radicals
producing hypoxia
temporarily inhibiting DNA synthesis, allowing
time for the repair enzymes to complete repair
of sublethal damage
forming disulphide bonds in proteins, thereby
strengthening them
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