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Molecular & Cellular Radiation Biology

Learning Unit 3 Presentation

Brad Johnson

on 11 April 2017

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Transcript of Molecular & Cellular Radiation Biology

Molecular & Cellular Radiation Biology
"DNA Repair" (cc) Courtesy of Tom Ellenberger, Washington University School of Medicine in St. Louis posted @ wikimedia commons
4 nitrogenous base pairs
adenine (A)
cystosine (C)
guanine (G)
thymine (T)
(A) only bonds w/ (T)

(C) only bonds w/ (G)
sequence constitutes genetic code
"DNA Double Helix" (cc) post by National Human Genome Research Institute @ wikimedia commons
hundreds of segments
2.9 billion base pairs
30,000 genes
46 chromosomes (23 pairs) per somatic cell
23 chromosomes per germ cell
visible during cell division - metaphase
Radiation Effects on DNA
Single-strand break
Double-strand break
Double-strand break in same rung
Covalent cross-links
single strand or side rail severed
chromosome not broken, but
DNA damaged = point mutation
repair enzymes can reverse damage
commonly occurs with low-LET radiation
1 or more breaks in sugar phosphate chain
not repaired as easily, could lead to further separation
occurs more commonly with high-LET radiation
2 hits within same rung
leads to broken chromosome
slight chance for repair
likely lead to impaired cell function or cell death
alteration of base sequence
loss or change of a base in DNA
may not be reversible
may cause incorrect genetic information to be passed on
spurlike molecules become "sticky"
can occur in many different patterns
all types are potentially lethal if not repaired
Radiation Effects on Chromosomes
changes in DNA = alteration of chromosome
may not always be observable
Broken-end rearrangement
Broken-end rearrangement
w/o visible damage
Radiation-induced chromosome breaks
2 or more fragments are produced
may be seen microscopically - metaphase & anaphase
affects somatic & genetic cells
break rejoins
how 95% of single-chromosome breaks mend
part of chromatid lost during next cell division
grossly mishapen chromosome produced
genetic material rearranged
Reference: Statkiewicz-Sherer MA, Visconti PJ, Ritenour ER. Radiation Protection in Medical Radiography.
Cellular Radiation Effects
Instant Death
Reproductive Death
(Interphase Death)
Mitotic Death
(Genetic Death)
Mitotic Delay
Interference of Function
1000 Gy
in seconds or minutes
Gross disruption of cell
1 - 10 Gy
Permanently lose ability to procreate
Prevents transmission of damaged data
Cells die without attempting division during interphase
Radiosensitivity determines dose required to produce effect
Relatively small dose required
Death occurs after 1 or more divisions
May occur at doses as small as 0.01 Gy
Cell exposed just before division, fails to start dividing on time
May resume normal function after delay
Radiation temporarily of permanently interferes with cell function
Survival Curves
Displays sensitivity of specific type of cell to radiation
Cells grown in Petri dish, then exposed to a specified dose
Data is collected on the number of cells forming new colonies
Radiation has different effects on different cells
More mature & specialized cell are less radiosensitive
Hematopoietic System
0.25 Gy delivered within a few days produces measureable hematologic depression
Most stem cells manufactured in bone marrow
Reduction in stem cells leads to reduction in mature cells
Greater dose to bone marrow, greater reduction in blood cells
Repopulation dependent on severity of dose
Humans exposed to whole body doses in excess of 5 Gy die within 30 - 60 days due to depletion of stem cells in this system
white blood cells
lymphocytes, neutrphils, granulocytes
recovery takes months
recovery takes months
platelet counts are monitored in rad therapy patients
1 - 10 Gy causes major depression
0.5 Gy causes major depression
Epithelial Tissues
Muscle Tissues
Nervous Tissues (Embryo-Fetus)
Reproductive Cells
Cells found in lining of:
respiratory tract
Highly radiosensitive due to proliferation rate
Specialized, do not divide
Low radiosensitivity
adult cells
specialized, do not divide
low radiosensitivity
very high doses can cause severe damage
more radiosensitive than adult
8-15 weeks "window of maximal sensitivity"
may lead to microcephaly and mental retardation
Mature spermatogonia, specialized, do not divide = low radiosensitivity
Immature spermatogonia, unspecialized, divide rapidly = high radiosensitivity
2 Gy= temporary sterility
5 - 6 Gy = permanent sterility
0.1 Gy
May cause genetic mutations, refrain from unprotected sex for a few months
may delay or supress menstruation
advised to postpone attempting conception for 30 days
Mature ova, low radiosensitivity
Immature ova, high radiosensitivity
400-500 mature ova produced from age 12-50
chromosome damage in male or female germ cells, may be passed onto offspring
AP L-spine ~ 0.0006 Gy
1.7 million xrays at once
AP L-spine ~ 0.0006 Gy
1700 - 17,000 xrays at once
AP L-spine ~ 0.0006 Gy
17 xrays at once
CT Head ~ 0.03 Gy
CT Head ~ 0.03 Gy
33-330 scans at once
CT Head ~ 0.03 Gy
33,000 scans at once
Molecular Effects of Radiation
Cellular Effects of Radiation
Cell Radiosensitivity
Radiation Energy Transfer Determinants
a million times smaller than a grain of sand...
Classification of Interaction
Direct vs. Indirect
Radiolysis of Water
Two hydrogen atoms walk into a bar...
80-85% Water
free radical*
single, unpaired e- in outer shell
extremely reactive

Target Theory
X-ray LET = 3 kEv/micron
X-ray RBE = 1
numerical description of O² effect
max value of 3 (x-rays), low value of 1 (alpha particles)
High LET
Nervous Tissues (Adult)
Higher Radiosensitivity
Lower Radiosensitivity
Law of Bergonie' & Tribondeau
Radiated testicular germ cells of rabbits
radiosensitivity was a function of the metabolic state of the cell
Law applies to all cells it states the following:

Reproductive Activity
Degree of Specialization
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