1. Biological effects of radiation

2. INTRODUCTION

3. • Radiation is all around us. It is naturally
present in our environment & comes from
outer space (cosmic), the ground (terrestrial),
and even from within our own bodies.
• Certain foods such as bananas and brazil nuts
naturally contain higher levels of radiation
than other foods.
• Levels of natural or background radiation can
vary greatly from one location to the next.

5. Typical Effective Radiation Dose from Diagnostic X Ray—Single Exposure

7. Typical Effective Radiation Dose from Nuclear Medicine Examination

8. • Radiation is of 2 types:
– Ionizing (α, β, γ & x-rays)
– Nonionizing (visible light, infrared, radiowaves)
• Ionizing radiation is subdivided into:
– electromagnetic radiation (X-rays and γ rays)
– particulate radiation (neutrons, alpha and beta
particles).

9. Radiation Biology History
• 1895-Roentgen announces discovery of X-rays
• 1896-(4 months later) Reports of skin effects
in x-ray researchers
• 1902-First cases of radiation induced skin
cancer reported
• 1906-Pattern for differential radiosensitivity of
tissues was discovered.

10. • Biological effects of ionizing radiation depend
on several factors that make them variable
and inconsistent.
• The effects are classified based on their nature
and timing after exposure into
– early or delayed,
– somatic or hereditary,
– stochastic or deterministic

12. Prompt Effects
• High doses delivered to the whole body of healthy adults within short
periods of time can produce effects such as blood component changes,
fatigue, diarrhea, nausea and death. These effects will develop within
hours, days or weeks, depending on the size of the dose. The larger the
dose, the sooner a given effect will occur.
Effect Dose
Blood count changes 50 rem
Vomiting (threshold) 100 rem
Mortality (threshold) 150 rem
LD50/60* (with minimal supportive care) 320 – 360 rem
LD50/60 (with supportive medical treatment) 480 – 540 rem
100% mortality (with best available treatment) 800 rem

13. Delayed effects:
• effects such as cataract formation and cancer
induction that may appear months or years
after a radiation exposure
*average lifetime risk of death from cancer following
an acute dose equivalent to all body organs of 0.1 Sv
(10 rem) is estimated to be 0.8%. baseline risk of
cancer induction in the United States is
approximately 25%.

14. Another way of stating this risk is by considering
the Relative Risk of a 1 in a million chance of
death from some common activities:
· Smoking 1.4 cigarettes in a lifetime (lung cancer)
· Eating 40 tablespoons of peanut butter (aflatoxin)
· Spending two days in New York City (air pollution)
· Driving 40 miles in a car (accident)
· Flying 2500 miles in a jet (accident)
· Canoeing for 6 minutes (drowning)
· Receiving a dose of 10 mrem of radiation (cancer)

16. • Stochastic effects refer to random and
unpredictable effects usually following chronic
exposure to low dose radiation. E.g.
Hereditary effects and carcinogenesis

17. Schematic development of the events leading to stochastic radiation effects

18. • Deterministic (non-stochastic) effects are non-
random and have a highly predictable
response to radiation. There is a threshold of
radiation dose after which the response is
dose-related. E.g. radiation-induced lung
fibrosis and cataract

19. MECHANISMS OF RADIATION
EFFECTS

20. Ionizing radiation exerts its effects on biological targets through two
major mechanism:

21. Direct effect
• ionizing radiation acts by direct hits on target
atoms.
• All atoms or molecules within the cells, such
as enzymatic and structural proteins and RNA,
are vulnerable to radiation injury but DNA is
the principal target, in which ionizing radiation
produces single or double-stranded
chromosomal breaks.

22. • It is estimated that about one third of
biological damage by γ radiation is caused by
direct effects.
• This process becomes more dominant with
high LET radiation, such as neutrons or α
particles

23. Indirect Effect
• two-thirds of biological damage caused by low
linear energy transfer (LET) radiation is due to
indirect action

24. • Water Radiolysis
absorption of energy depends on the abundance
of material in the path of the radiation. Water is
the most predominant molecule in living
organisms, therefore, a major proportion of
radiation energy deposited will be absorbed in
cellular water.
A complex series of chemical changes occurs in
water after exposure to ionizing radiation. This
process is called water radiolysis

26. • These primary water radicals have high reactivity
towards molecules of cells, DNA, lipids and other
subcellular constituents. In oxygenated solutions,
hydrogen atoms can react with oxygen to give
hydroperoxyl free radicals(HO2•)
• The relative yields of the water radiolysis products
depend on the pH and LET of the radiation.
• The concentration of these radicals are expressed in
terms of a G value which is defined as the number of
radicals or molecules produced per 100 eV of energy
absorbed in the medium

27. FACTORS AFFECTING RADIATION
HAZARD

28. Factors Related to Ionizing Radiation
• Type of Radiation:
– Various types of radiation differ in penetrability
based on LET.
– This value is high for alpha particles, lower for
beta particles, and even less for gamma rays and
X-rays. Thus alpha particles penetrate a short
distance but induce heavy damage,

29. • Mode of Administration:
– a single dose of radiation causes more damage
than the same dose being divided (fractionated)
• Dose Rate:
– The longer the duration for the same total dose,
the better the chance of cellular repair and the
smaller the damage

30. Factors Related to Biological Target
• Radiosensitivity:
– Radiosensitivity varies with the rate of mitosis and
cellular maturity. Blood-forming cells are very
sensitive to radiation, while neurons, muscle and
parathyroid cells are highly radioresistant. With in a
given cell, the nucleus in general is relatively more
radiosensitive than the cytoplasm.
– When cells in G0/G1phase of the cell cycle are
exposed to radiation they tend to halt their
progression into G2/M phase. G2 synchronization
produces a cluster of radiosensitive cells. A second hit
within a time frame of 5–12 h leads to a higher
proportion of deleterious effects.

31. • Repair Capacity of Cells:
• Cell-Cycle Phase:
– All phases of the cell cycle can be affected by ionizing radiation.
Overall, sensitivity appears to be greatest in G2 phase.
– Recovery from sublethal damage occurs in all phases of the cell
cycle. However, this is most pronounced in the S phase, which is
also the most radio-resistant phase
• Degree of Tissue Oxygenation:
– Molecular oxygen is known to have the ability to potentiate the
response to radiation

32. MOLECULAR AND CELLULAR
RADIOBIOLOGY

33. Radiation lesions in DNA
• Radiation causes a wide range of lesions in
DNA such as
– single strand breaks in the phosphodiester linkage,
– double strand breaks on opposing sites or
– base damage,
– protein-DNA crosslinks and protein-protein
crosslinks involving nuclear proteins such as
histones and non-histone proteins.

34. • The number of DNA lesions generated by
irradiation is large, but the number giving rise
to cell kill is extremely small. The numbers of
lesions induced in the DNA of a cell by a dose
of1-2 Gy are approximately:
– base damages > 1000;
– single strand breaks (ssb) ~1000;
– double strand breaks (dsb) ~40.
• Dsb play a critical role in cell killing

35. Fate of Irradiated Cells
• No effect.
• Division Delay
• Apoptosis: cell death before it can divide.
• Reproductive Failure: cell death when attempting
MITOSIS.
• Genomic Instability: delayed reproductive failure.
• Mutation: cells contains mutation in genome.
• Transformation: mutation leads to carcinogenesis.
• Bystander Effects: damaged cell induces damage in
surrounding ones.
• Adaptative Response: increased resistance to radiation.

36. • Genomic Instability:
– Maximal radiation-induced genetic damage is
formed shortly (minutes to hours) after radiation
exposure. Nevertheless, it has been observed that
not only the irradiated cells but also descendents
may show delayed effects.
– Cells that sustain non-lethal DNA damage show
increased mutation rate in descendent cells
several generations after the initial exposure

37. • Bystander Effect.
– The cells in the vicinity of irradiated cells show
effects that cannot be attributed to targeting by
ionizing radiation tracks. The mechanism is not
clearly understood; however, gap junctional
intercellular communication or release of soluble
factors (such as cytokines) from irradiated cells
has been proposed. Through cell-to-cell
interaction, the directly irradiated cells
communicate with adjacent cells and spread the
effect of radiation to a larger number of cells.

38. Acute effects of radiation

39. • Acute Radiation Syndrome (ARS) is an acute
illness caused by irradiation of the entire body
(or most of the body) by a high dose of
penetrating radiation in a very short period of
time (usually a matter of minutes)

40. • conditions for Acute Radiation Syndrome (ARS) are:
• The radiation dose must be large (i.e., greater than 0.7 Gray (Gy)).
– Mild symptoms may be observed with doses as low as 0.3 Gy or 30 rads.
• The dose usually must be external ( i.e., the source of radiation is
outside of the patient’s body).
– Radioactive materials deposited inside the body have produced some ARS
effects only in extremely rare cases.
• The radiation must be penetrating (i.e., able to reach the internal
organs).
– High energy X-rays, gamma rays, and neutrons are penetrating radiations.
• The entire body (or a significant portion of it) must have received the
dose.
– Most radiation injuries are local, frequently involving the hands, and these
local injuries seldom cause classical signs of ARS.
• The dose must have been delivered in a short time (usually a matter
of minutes).
– Fractionated doses are often used in radiation therapy. These are large
total doses delivered in small daily amounts over a period of time.
Fractionated doses are less effective at inducing ARS than a single dose of
the same magnitude.

41. stages of ARS
• Prodromal stage (N-V-D stage): The classic symptoms for
this stage are nausea, vomiting, as well as anorexia and
possibly diarrhea (depending on dose), which occur from
minutes to days following exposure. The symptoms may
last (episodically) for minutes up to several days.
• Latent stage: In this stage, the patient looks and feels
generally healthy for a few hours or even up to a few
weeks.
• Manifest illness stage: In this stage the symptoms depend
on the specific syndrome and last from hours up to several
months.
• Recovery or death: Most patients who do not recover will
die within several months of exposure. The recovery
process lasts from several weeks up to two years

42. three classic ARS Syndromes
• Bone marrow syndrome (aka: hematopoietic syndrome) occur with a dose
between 0.7 and 10 Gy (70 – 1000 rads) though mild symptoms may occur
as low as 0.3 Gy or 30 rads.
– The survival rate of patients with this syndrome decreases with increasing
dose. The primary cause of death is the destruction of the bone marrow,
resulting in infection and hemorrhage.
• Gastrointestinal (GI) syndrome: occur with a dose greater than
approximately 10 Gy (1000 rads) although some symptoms may occur as
low as 6 Gy or 600 rads.
– Survival is extremely unlikely with this syndrome. Destructive and irreparable
changes in the GI tract and bone marrow usually cause infection, dehydration,
and electrolyte imbalance. Death usually occurs within 2 weeks.
• Cardiovascular (CV)/ Central Nervous System (CNS) syndrome: occur with
a dose greater than approximately 50 Gy (5000 rads) although some
symptoms may occur as low as 20 Gy or 2000 rads.
– Death occurs within 3 days. Death likely is due to collapse of the circulatory
system as well as increased pressure in the confining cranial vault as the result
of increased fluid content caused by edema, vasculitis, and meningitis

44. Cutaneus radiation syndrome
• It is possible to receive a damaging dose to the skin without
symptoms of ARS, especially with acute exposures to beta radiation
or X-rays. Sometimes this occurs when radioactive materials
contaminate a patient’s skin or clothes.
• When the basal cell layer of the skin is damaged by radiation, within
a few hours after irradiation, a transient and inconsistent erythema
(associated with itching) can occur. Then, a latent phase may occur
and last from a few days up to several weeks, when intense
reddening, blistering, and ulceration of the irradiated site are
visible.
• In most cases, healing occurs by regenerative means; however, very
large skin doses can cause permanent hair loss, damaged
sebaceous and sweat glands, atrophy, fibrosis, decreased or
increased skin pigmentation, and ulceration or necrosis of the
exposed tissue.

46. Initial Treatment and Diagnostic
Evaluation
• Treat vomiting, and repeat CBC analysis, with
special attention to the lymphocyte count,
every 2 to 3 hours for the first 8 to 12 hours
following exposure (and every 4 to 6 hours for
the following 2 or 3 days).
• Sequential changes in absolute lymphocyte
counts over time are demonstrated in the
Andrews Lymphocyte Nomogram

47. From Andrews GA, Auxier JA, Lushbaugh CC. The Importance of Dosimetry to the Medical
Management of Persons Exposed to High Levels of Radiation.
In Personal Dosimetry for Radiation Accidents. Vienna :
International Atomic Energy Agency; 1965

48. • Patients with a minimal lymphocyte count (MLC) of 1000-
1499/mm3 have an approximate absorbed dose of 0.5-1.9
Gy. prognosis is good because the absorbed dose is usually
nonlethal.
• Patients with MLC of 500-999/mm3 have an approximate
absorbed dose of 2.0-3.9 Gy. fair prognosis.
• MLC of 100-499/mm3 coincides with an approximate
absorbed dose of 4.0-7.9 Gy. poor prognosis,
• MLC less than 100/mm3 have an estimated absorbed dose
of greater than 8 Gy. high incidence of death despite bone
marrow stimulation.
• Survival has not been documented for those exposed to
greater than 10 Gy.

49. • Time to emesis:
– Time to emesis (TE) correlates with exposure
dose, decreasing as exposure dose increases.
– For TE less than 1 hour, whole-body dose
estimates are greater than 4 Gy.
– For TE between 1 and 2 hours, whole-body dose is
estimated to be greater than 3 Gy.
– for TE greater than 4 hours, whole-body dose is
estimated to be around 1 Gy.

50. Pharmacologic Therapy for Radiation
Injury
• Enteral binding agents
– Barium sulfate: Adult dose: 200 mL PO x 1 dose
Binds with strontium and radium
– Aluminum and magnesium salts: Adult dose: 100
mL PO x 1 dose. Binds with strontium, radium, and
phosphorous
– Activated charcoal

51. • Blockade of end-organ uptake
– Potassium iodide: Adult dose: 130 mg PO daily (maximum: 1
dose in 24h)
Duration of therapy: Continue daily dose until exposure risk has
passed and/or until other measures (eg, evacuation, sheltering,
control of the food and milk supply) have been successfully
implemented
Blocks thyroid uptake of iodine and technetium
– Calcium gluconate: Adult dose: 3 g IV x 1 dose
Blockade into bone by increasing urinary excretion of
radioactive strontium and calcium
– Calcium chloride: Adult dose: 1 g IV x 1 dose
Blockade into bone by increasing urinary excretion of radioactive
strontium and calcium

52. • Dilution
– Oral fluids: Adult dose: 5-10 L PO/IV daily x 1wk
Excretion of tritium
– Neutra Phos: Adult dose: 1 packet (diluted) PO
QID x 3d. Excretion of phosphorus
– K Phos: Adult dose: 2 tablets PO QID x 3d.
Excretion of phosphorus

53. • Chelation
– Pentetate trisodium salts(DTPA; Ca-DTPA within
24h, Zn-DTPA after 24h): Adult dose: 1 g IV in 250
mL saline/D5W daily. Chelates americium,
uranium, plutonium, heavy metals
– Penicillamine: Adult dose: 250-500 mg PO QID.
Chelates cobalt
– Prussian blue: Adult dose: 3 g PO TID; minimum
30-day treatment. Chelates cesium and thallium

54. • Decrease organ damage
– Sodium bicarbonate: Adult dose: 2 mEq/kg IV x 1
dose. Nephroprotective for uranium

55. RADIATION AND PREGNANCY

56. Acute Radiation Time Post Conception
Dose* to the Blastogenesis Organogenesis Fetogenesis
(up to 2 wks) (2 –7 wks) (8–15 wks) (16 –25 wks) (26 –38 wks)
Embryo/Fetus
< 0.05 Gy (5 rads)† Noncancer health effects NOT detectable
0.05–0.50 Gy (5–50 rads) Incidence of failure to • Incidence of • Growth retardation possible
implant may increase major
slightly, but surviving malformations • Reduction in IQ possible (up to
embryos will probably may increase 15 points, depending on dose)
have no significant slightly Noncancer health
(noncancer) health effects • Incidence of severe mental effects unlikely
• Growth retardation up to 20%, depending
retardation on dose
possible
> 0.50 Gy (50 rads) Incidence of failure to • Incidence of • Incidence of miscarriage • Incidence of Incidence of
implant will likely be miscarriage may probably will increase, depending miscarriage may miscarriage
The expectant mother large,‡depending on dose, increase, on dose increase, depending on and
may be experiencing but surviving embryos will depending on dose neonatal
acute radiation syndrome probably have no dose • Growth retardation likely death will
in this range, depending significant (noncancer) • Growth retardation probably
on her whole-body dose. health effects • Substantial risk • Reduction in IQ possible (> 15 possible, depending on increase
of major points, depending on dose) dose depending o
malformations
such as • Incidence of severe mental • Reduction in IQ
neurological and retardation > 20%, depending on possible, depending on
motor dose dose
deficiencies
• Incidence of major • Severe mental
• Growth malformations will probably retardation possible,
retardation likely increase depending on dose
• Incidence of major
malformations may
increase

57. Estimated Risk for Cancer from Prenatal Radiation Exposure
Radiation Dose Estimated Childhood Estimated Lifetime‡ Cancer Incidence§
Cancer Incidence* † (exposure at age 10)
No radiation exposure 0.3% 38%
above background
0.00–0.05 Gy (0–5 rads) 0.3%–1% 38%–40%
0.05–0.50 Gy (5–50 1%–6% 40%–55%
rads)
> 0.50 Gy (50 rads) > 6% > 55%
* Data published by the International Commission on Radiation Protection.
† Childhood cancer mortality is roughly half of childhood cancer incidence.
‡ The lifetime cancer risks from prenatal radiation exposure are not yet known. The lifetime risk
estimates given are for Japanese males exposed at age 10 years from models published by the United
Nations Scientific Committee on the Effects of Atomic Radiation.
§ Lifetime cancer mortality is roughly one third of lifetime cancer incidence.

58. RADIATION HORMESIS:

59. introduction
• There are threevmodels predicting
relationships between the radiation dose and
the effect of such an expo-sure to a biological
target.
• The differences between these models arise
from different underlying assumptions

60. • Linear-No Threshold Model: It assumes that any
level of radiation is harmful and that the risk increases linearly
with increments of dose. It is applied for radiation protection
purposes and is meant to limit the risk to workers in radiation
fields.

62. • ThresholdModel: It assumes that the risk of radiation
is linearly related to the dose; however, this occurs only after
a certain threshold level is exceeded. Below the threshold
level no risk is to be expected. The theory behind the
threshold level is that some degree of cellular damage should
accumulate and produce cell damage.

63. • Hormesis Model: In this model there is a bimodal effect
of radiation, where below a certain threshold level radiation is
protective, and harmful effects are seen only when this
threshold is exceeded. The rationale is that radiation at low
levels induces protective cellular mechanisms which prevent
DNA damage occurring spontaneously or due to other
stresses

64. definition
• Hormesis is a concept that describes the
nature of dose-response relationships in
biological systems as displaying a stimulatory
response at low doses and an inhibitory
response at higher doses.

65. • The probability of radiation induced adaptive
protection measurably outweighs that of
damage from doses well below 200 mGy low-
LET radiation.

67. Note that mechanisms of DNA damage prevention and repair and the immune stimulation
decrease after a maximum at doses between 0.1 Gy and 0.2 Gy, in contrast to apoptosis
incidence that increases with dose

68. Single low-dose induced adaptive responses have dif-ferent times of duration depending on
protective mechanisms that begin with a delay of several hours and may last for days
to weeks – and even up to months for immune response. Note that repair in response to
radiation damage begins immediately after damage has occurred.