Radiobiology is the study of the biological effects of radiation. The document summarizes key concepts in radiobiology including: 1. The law of Bergonie and Tribondeau which states that radiosensitivity depends on the metabolic state of irradiated tissue. 2. Factors that affect radiosensitivity including linear energy transfer, relative biological effectiveness, and protraction and fractionation of radiation doses. 3. Effects of radiation at the molecular, cellular, tissue and organism levels including DNA damage, cell death, tissue damage, and increased risk of cancer and genetic mutations. 4. Classification of deterministic effects which have thresholds and increase in severity with higher doses, and stochastic effects where risk increases

1. RADIOBIOLOGY
Anjan Dangal
BS Medical Imaging , Final Year
National Academy of Medical Sciences,
Bir Hospital, Kathmandu, Nepal

2. Contents
• Law of Bergonie and Tribondeau
• Factors affecting Radiosensitivity
• Radiation effects on molecular and cellular level.
• Radiation effects on tissue/organ level.
• Deterministic and Stochastic Effects.

3. LAW OF BERGONIE AND TRIBONDEAU
• Theorized and observed by Bergonie and Tribondeau: Radiosensitivity
is a function of the metabolic state of tissue being irradiated.

5. Physical Factor affecting Radiosensitivity
• Linear Energy Transfer (LET)
• Relative Biological Effectiveness(RBE)
• Protraction and Fractionation

6. Physical factors that affect radiosensitivity
1. Linear energy transfer (LET): is a
measure of the rate at which energy is
transferred from Ionizing radiation to
soft tissue.
• Expressed in units of kiloelectron volt
of energy transferred per micrometer
of track length.
• Higher LET increases the ability of
ionizing radiation to produce a biologic
effect and the probability of interaction
with target molecule.

7. • Relative Biologic Effectiveness:

8. Protraction and Fractionation
• If a dose of radiation is delivered over a long period of time rather
than quickly, the effect of that dose is less.
• Protraction: Dose is delivered continuously but at a lower dose rate.
• Fractionation: Dose is delivered with some interval and fraction but at
a same dose rate.
Dose protraction and fractionation causes less effect because
time is allowed for intracellular repair and tissue recovery.

9. Biologic Factors That Affect Radiosensitivity
• Oxygen Effect:Oxygen Effect: Tissue is more sensitive to radiation when
irradaited in the oxygenated state than when irradiated under anoxic or
hypoxic conditions. Diagnostic X- ray Imaging is performed under the
conditions of full oxygen.
• Age
• Others:
• Recovery: Intracellular repair + Repopulation
• Chemical Agent: Radiosensitizer (halogenated pyrimidines) and Radioprotective agents
(cysteine and cysteamine).
• Hormesis: a little bit of radiation is good for you !

10. •Radiation Effects on the molecular/ cellular level
1. Targets of Biological Effects of Radiation
2. Radiation Induced DNA Damage and cellular radio responses.
3. Mutation
•Radiation Effects on Tissue/ Organism
1. Classification of Radiation exposure and its effects on Human Body
2. Radio sensitivity of cells and tissues
5/2/2021 10

11. MOLECULAR RADIOBIOLOGY
MOLECULAR COMPOSITION OF THE BODY:
• Water 80%
• Protein 15 %
• Lipids 2 %
• Carbohydrates 1 %
• Nucleic Acid 1%
• Others 1 %
Even though the initial interation between radiation and tissue occurs at the electron
level, observable human radiation injury results from change at molecular level.
DNA is the most
radiosensitive
molecule, is not
abundant in the cell.

12. Subsequent studies revealed
that the major target of radiation
is
DNA
The Biological Effect of radiation is strongly
influenced by DNA
damage and its repair after irradiation
Targets of Biological Effects of Radiation
5/2/2021 12

13. • Orders of Frequency:
1. Damaged base only.
2. Damage that cause break of one strand.
3. Damage that causes two strands at the same location to
break
Radiation induced DNA Damage
5/2/2021 13

14. Cell Response to radiation Exposure
DNA
RNA
Protein
Normal Cell Function
radiation
DNA Damage
Stop of cell proliferation
Synthesis of repair Enzymes
DNA damage and its repair
Repairable
Cell death
2.Radiation Induced DNA Damage and cellular radio responses.
5/2/2021 14

15. • DNA molecule can be damaged without the production of a visible chromosome
aberration. Although reversible but can also lead to cell death. If enough cells of
same type respond similarly, then a particular organ or tissue can respond: This
describes the cause of deterministic effect.
• Damage to DNA can also result in abnormal metabolic activity. Uncontrolled
rapid proliferation of cells may occur, which is the reason for radiation induced
malignant disease: cause of stochastic effect.

16. Examples of Chromosomal Abnormalities
Radiation
Translocation
Inversion
Deletion
Normal
Dicentric
5/2/2021 16

17. • As the human body is an aqueous solution that contains 80% water
molecules, radiation interaction with water is the principal molecular
interaction in the body.
• When water is irradiated, it
disassociates into other molecule
product: this action is called
radiolysis of water.

18. The Cell Cycle and Radiation sensitivity
• Radiosensitivity of cells, differ depending on the
phase of the cell cycle. This is referred to as a
"cell cycle dependence" of radiosensitivity.
• The relationship between the cell cycle and
radiation sensitivity is shown in the graph below
• Early G1 phase: low sensitivity
• Late G1 phase to early S phase:
high sensitivity
• Late S phase to G2 phase: low
sensitivity
• M phase: high sensitivity
Cell division
5/2/2021 18

19. • Radiation just like chemical substance and viruses , has the ability to induce
mutation.
• Mutations in the somatic cells increases the risk of cancer
• Mutations in reproductive cells increases the risk of cancer , and may be
transmitted to future generations as genetic Effects
Reproductive
Cell mutation
Cancer
Genetic effects
Radiation
Somatic cell mutation
3. Mutation
5/2/2021 19

20. Effects of radiation on the Human Body
Genetic effects
Effects on the embryo and
fetus
( Mental retardation)
Acute effects
( erythema, hair loss)
Late effects : cataracts
(cancer, leukemia )
Harmful Tissue reactions
( Somatic Effects)
Hereditary disorder
( congenital anomalies)
5/2/2021 20

21. Types of Radiation Damage
• Acute effects ( Acute radiation damage)
1. These appear, at the least , after 2 to 3 months of exposure.
2. The casual relationship with radiation is easy to find.
( Examples) Death, leukopenia, skin reactions
• Late effects ( Late radiation damage )
1. These appears after a long incubation period following exposure.
2. The casual relationship with radiation is often difficult to find.
(Examples) Cancer, genetic effects, cataracts, growth failure.
B.1, Classification of radiation exposure and its effects on human body
5/2/2021 21

22. Radiosensitivity of Tissues and Organs
( Principle) High cell division frequency = high sensitivity
Radiation
sensitivity
Tissue/ Organ
Highest Lymphoid tissue ( thymus, spleen)
Bone marrow
Gonads ( testes) ( spermatogonia), ovary ( oocyte)
High Small intestine epithelium, mucuos membranes,
skin epithelium, capillaries,eye lens, hair follicles
Medium Kidney, liver, lung, salivary gland
Medium to low Thyroid, pancreas, adrenal gland, muscle, connective tissue
Lowest Bone, fat, nerve cells
B.2. Radiosensitivity of the cells and tissues
5/2/2021 22

23. Classification of biological effect of radiation
• The Biological effects of radiation are divided into deterministic effects and
stochastic effects
Threshold
Dose
As the exposed dose
increases
Damage
Deterministic
Effects
Yes Seriousness increases Excluding stochastic effects,
All harmful tissue reactions
Stochastic
Effects
No Frequency of occurrence
increases
Genetic Influence,
carciogenesis
Dose
Dose
Threshold dose
Deterministic Effects Stochastic Effects
5/2/2021 23

24. Deterministic Effects Of Radiation
• Deterministic radiation responses are those that exhibit increasing
severity with increasing radiation dose.
• There is dose threshold and dose response relationship is nonlinear.

25. Deterministic Effects
• Deterministic effects are caused by the cell death.
Symptoms do not appear at a dose that does not cause a certain level of cell death
If the dose of radiation exposure is less than the
threshold dose. It will not cause damage ( symptoms)
Examples: death of the individual,
cataracts,
damage to skin,
damage to intestinal epithelial cells,
damage to bone marrow, etc
Probability of having an effect
5/2/2021 25

27. Acute Radiation Lethality
• The sequence of events following high level radiation exposure
leading to death within days or weeks is called the acute radiation
syndrome.

28. Local Tissue Damage
• Follow a threshold type dose response
relationship.
• When threshold exceeded, the severity
of response increases with increasing
radiation dose in non-linear fashion.

29. Effects on the Skin

30. Effects on Gonads
• The cells of the testes (the male gonads) and the ovaries (the female
gonads) respond differently to radiation because of differences in
progression from the stem cell to the mature cell.
• The most radiosensitive cell during female germ cell development is
the oocyte in the mature follicle.
• The Spermatogonial stem cells signify the most sensitive phase in the
gametogenesis of the spermatozoa. Spermatocytes and spermatids
are relatively radiosensitive.

31. Effects on Gonads

32. Effects of Radiation on Gonads: Testicles and Ovaries
Radiation damage to the testes
0. 15 Gy of radiation exposure leads to temporary
Infertility
(due to decreased sperm count)
3.5 – 6 gy of acute radiation exposure leads to permanent
infertility
Chronic exposure of 2 Gy/year or more radiation causes
permanent infertility.
Radiation sensitivity
5/2/2021 32
1.5 Gy of acute exposure causes temporary
infertility and stops menstruation
2.5 – 8 Gy of acute radiation exposure leads to
permanent infertility

33. Effects of radiation on the gastrointestinal Tract
• The duodenum is the most
Radiosensitive part in the GI tract.
• The crypt cells ( stem cells, proliferation
Cells) in intestinal glands are especially
Sensitive to radiation.
• 10 Gy or more of radiation exposure will stop proliferation of crypt cells, and as
mature epithelial cells reach the end of their life, the submucosal tissues are
exposed.
• Tissue damage by radiation causes dehydration due to diarrhea, bleeding, and
abdominal pains. If the damage is severe, it leads to death.
5/2/2021 33

34. Effects of Radiation on mouse small Intestine
Normal 15 Gy
5/2/2021 34

35. Death by bone marrow damage
( 2.5 – 10 Gy)
Damage to hematopoietic stem cells and lymphocytes death in 1-2
months after radiation exposure mainly due to infection and
hemorrhage as a result of the loss of blood cells
Decrease in Bone marrow cells due to exposure of 10 Gy.
Normal 10 Gy

36. Hemopoietic System

37. Lymphocytes are the most radiosensitive whereas
Erythrocyte are the less radiosensitive.

40. Estimated Fetal Dose From Imaging

41. STOCHASTIC EFFECTS
• Stochastic effects of radiation are low doses delivered over a long period.
• The principal stochastic effects of low dose radiation over long period
consists of radiation induced malignancy and genetic effects.
• Effect has an increased likelihood with increasing exposure, but no
threshold.
• Due to DNA mutations which increase the probability of developing cancer.
• Relevant to routine clinical imaging, but risk remains low.
• Example: Leukemia, Lymphoma, Radiation induced sarcoma, Thyroid
cancer, breast and ovarian cancer.

42. Stochastic Effects
• Stochastic effects are caused by mutant cells.
• If even one mutant cell appears,
it may cause the effects of radiation.
If the dose of radiation increases
the probability of effects also increases
Stochastic effects mean
that even low levels of
radiation exposure do not
guarantee safety.
Examples: Carcinogenesis, genetic influence
Probability of having an effect
5/2/2021 42

43. LOCAL TISSUE EFFECTS
• SKIN:
Chronic irradiation of skin can result in severe non-malignant changes.
Radiodermatitis: tight and brittle appearance with severe crack.
• Chromosomes:
Low dose of radiation can produce chromosome abberation that may not be
apparent untill many years of radiation exposure.
• Cataracts:
The radiosensitivity of the lens of the eye is age dependent. As the age of the
individual increases, the radiation effect becomes greater and the latent period
becomes shorter. Latent periods ranging from 5 to 30 years have been observed in
humans, and the average latent period is approximately 15 years. If the lens dose is
high enough, in excess of approximately 10 Gyt (1000 rad), cataracts develop in
nearly 100% of those who are irradiated.

44. Most investigators would suggest
that the threshold after an acute x-
ray exposure is approximately 2 Gyt
(200 rad).
In computed tomography, the lens
dose can be 50 mGyt (5 rad).
• LIFE SPAN SHORTENING:
humans can expect a reduced life
span of approximately 10 days for
every 10 mGyt.

45. Risk of carcinogenesis from small doses of
radiation exposure
• 100 mSv or more of radiation exposure causes a significant
increase in the risk of carcinogenesis.
• At 100 mSv or less exposure , it is impossible to observe clear –
cut effects because of changes in risk due to other factors.
5/2/2021 45

46. Genetic Effects
• We do not have any data that suggests that radiation induced genetic
effects occur in humans.
• Radiation induced mutations are usually harmful.
• For most pre-reproductive life, the woman is less sensitive than the
man to the genetic effects of radiation.
• Most radiation induced mutations are recessive. These require that
the mutant genes must be present in both the male and female to
produce the triat.

47. Thankyou

48. References
• Book: Radiologic Science for Technologist, Stewart Carlyle Bushong,
11th Edition.
• MOOC: An Introduction to Radiation and Radioactivity, Hokkaido
University, Japan