2. Needful definitions
LET: (Linear Energy Transfer)
The energy released per micron medium along the track of
any ionizing particle
LET Q2/V2
Slow moving and high charged particle High LET(KeV/μm)
Fast moving and low charged particle Low LET(KeV/μm)
Particle Charge Energy LET (keV/μm)
Proton +1 Small 92
Proton +1 2MeV 16
Alpha +2 Small 260
Alpha +2 5MeV 95
3. Needful definitions
RBE: (Relative Biological Effectiveness)
It is the ratio of the 250KV X ray dose that produces
specific biological effect to the test dose of any radiation that
produces the same effect.
It is related to LET
RBE = 250 KV X ray dose/Tested dose of any radiation
For Ex. RBE of 3 means, 3 Gy of standard radiation is needed to
achieve the same cell kill as 1 Gy of test radiation
Overkill effect: A single particle deposits much more energy
than is required to kill a cell. Therefore, it kills less cells per
absorbed dose.
• OER strictly decreases as LET increases.
LET<1 keV/μm: OER=2.5–3.5
LET>100 keV/μm: OER=1.0
4. Relation:
As LET increases, RBE increases until it reaches a peak at 100 keV/μm.
Decreased repair due to high density of ionizations.
Increased direct action, less oxygen dependent.
100 keV/μm corresponds to one ionization per 2 nm, which is the
diameter of a DNA strand, and is considered the optimal LET for cell
killing.
The biological effect is directly proportional to LET of radiation
5. Introduction - cell
Cell is the structural and functional unit of all living organisms
Cells are generally classified into two types:
•Somatic cells
•Germ cells
Cell doesn’t grow indefinitely in size, instead at a certain time, it
goes to divide and produces two daughter cells.
Two types of cell division may be mitotic or Meiotic
Germ cells are formed by Meiosis where as somatic cells are
formed through mitosis division
cell exhibits two phases in its life time:
•Inter-phase
•Mitosis phase
7. CELL CYCLE
Mitotic Phase is divided into 4 phases such as:
Prophase
Metaphase
Anaphase
Telophase
Inter phase is the longest phase & classified into 4 stages:
G1 Phase: Divisible cell growth
S Phase : Protein Synthesis and DNA duplication
G2 Phase: Organelles doubles and prepares cell to division
G0 Phase: Delays cellular activities in case of difficulties
during developing stages
The Effects of radiation on cell is majorly depends on which
phase of cell. Early G2 and M stages are most radio-sensitive
where as G1 and S phases are radio-resistive.
8. The effect of radiation on cell causes
various effects such as
•Cell may apoptotic (loss of
proliferative capacity)
•mitotic death
•cell may survive ( Retain of
reproductive capacity)
DNA resides inside the cell nucleus,
is the principle target for biological
effects of radiation
DNA is a large molecule with well
known double helix structure, consists
of two strands, held together by
hydrogen bonds between the bases
Effects of Radiation on Cell
10. When DNA is damaged by radiation, basic function of cell is
altered results,
1. death of cell
2. Abnormal modification of cell function.
Irradiation can results various types of damages in which part of
DNA is affected by radiation
1. Strand breaks
2. Alteration to bases
3. Destruction of sugars
4. Cross links and formation of dimmer
Radiation have direct or indirect effects of DNA molecules
11. Direct Effects:
Interaction of ionizing radiation
directly with DNA is named as direct
effect.
Atoms in DNA may ionized or
excited which leads to biological
change.
When DNA directly affected by
radiation, energy absorbed by DNA
undergoes to Strand breaks
Direct Effect is proportional to LET of
Radiation.
A quarter to a third of the damage
produced in cellular macro-molecules
by radiation is due to its direct effect.
12. Indirect Effects:
Interaction of ionizing radiation
happens with other molecules or
atoms rather than DNA is named as
indirect effect.
Most Probable Phenomena due to
70% of water composition of human
body
Radiation interacts water molecules
results free radical generation
OHHOHOHe
OHHOH
eOHOH
22
2
22
13. Indirect Effects:
Due to short life span (10-10sec),
combines with O2 and forms H2O2
and HO2 with life time of 10-5sec
Those can’t move due to little
dense, prevents nutrition of
neighbouring cells by oxidization
Finally results cell death through
nutritive deficiency or isolation of
these cells from other tissues
Two third of the damages
caused by in this effect.
14. Molecular Level effects
Strand Breaks (Single or Double)
1. Breaks of Phosphate di-ester bond or deoxyribose.
2. Single Strand Breaks (SSB) are little biological
consequence where as Double Strand Breaks (DSB)
results cell killing or Carcinogenesis or Mutation
3. As X ray dose of 1 – 1.5 Gy produces about 1000 SSBs
and 50 – 100 DSBs
4. SSBs are directly proportional to dose (0.2 – 60000 Gy)
5. When come to DSBs, the relation with dose is dispute
(linear quadratic relation)
15. Alteration of Bases
1. Bases can be partially destroyed or chemically modified
2. Two or three of base alterations can be seen for 10 SSB
Destruction of Sugars
1. Alteration of deoxy-ribose are rarer and not well
understood.
2. Only 0.2 to 0.3 alterations of sugars per 10SSBs have
identified
Cross links and Formation of dimmers
16. Cellular Level Effects
Inhibition of division
- cell division is inhibited/delayed
Chromosome aberrations
- structure or number of chromosome altered
Gene mutation
- DNA sequence of A,T,G,C bases altered
Cell Killing/cell death
- cell stops dividing or functioning
17. Chromosomal Aberrations:
When cells are irradiated with X rays, DBSs are produced in
chromosomes and broken ends appear to be sticky and can rejoin with
any other sticky end in variety of ways
1. Breaks may restitute
2. Breaks may fails to rejoin and give rise to an aberration (deletion
of next mitosis)
3. Broken ends may re-assort and rejoin with other ends and rise
to distorted chromosomes follows next mitosis
Usually aberrations seen at interphase and lethal to cells in three
different ways:
1. Di-centric
2. Ring
3. Anaphase Bridge
18. Types of Effects
The effects of radiation in human body are classified into two
depends on which cells are damaged.
Somatic effects – Arises from damage to somatic cells
• Majorly depends on dose, fractionation & volume
irradiated
•affect only exposed individual
Genetic effects – Arises from damage of reproductive cells
and manifest in the progeny of exposed person
These effects may be either Early or Late
May appear immediately (few hours to weeks) after exposure or
appear much later (years or decades) after exposure
19. Early effects:
Acute exposures causes early effects
Usually found in high proliferative cells like bone marrow
epidermis
Starts with vascular changes, clinically visible as erythema.
Eventually, healing occurs based on surviving stem cells
After irradiation, each of he cells in a given tissue has a certain
probability of being killed and this probability increases with dose.
20. THRESHOLD DOSE SYMPTOMS
1 Gy Nausea
Vomiting
Diarrhea
Fatigue
Headache
Lack of appetite
Time of appearance & severity
Depends on dose. Within 1-24 hours
Consequences
Person recovers within 1-2 days
Radiation Sickness
21. THRESHOLD DOSE SYMPTOMS
3 to 5 Gy Anemia
Infection
Fever
Hemorrhage
Time of appearance & severity
Depends on dose. Within 1 to 2 months
Consequences
LD50/60
Time of death after exposure 30 – 60 days
Bone Marrow Syndrome
22. THRESHOLD DOSE SYMPTOMS
5 to 15 Gy Damage to Small Intestine
Poor Food intake
Less nutrition absorption
Diarrhea, Ulceration & Low BP
Circulatory collapse
Consequences
Death between 1 – 2 weeks
Gastro Intestine Syndrome
23. THRESHOLD DOSE SYMPTOMS
>15 Gy Coma
Tremors
Ataxia
Convulsions
Delirium
Time of appearance & severity
within few hours dose dependent
Consequences
Death in <5 days dose dependent
CNS Syndrome
24. Dose Range Effect
<0.1Gy Chromosomal Aberrations detectable
<0.5GY Transient reduction in WBC
Temporary Sterility in males
<1.0Gy NVD Syndrome
<3.0Gy Damage of BM, Lymph nodes , Spleen;
Death in 4 to 8 weeks (10%)
<5.0Gy LD50/60
<15.0Gy Gastro-intestinal syndrome
death in 1-2 weeks (100%)
>15.0Gy CNS syndrome
death in few hours to days
Early Somatic effects due to acute whole body exposures due to
Low LET
25. Dose Range Region Effect
0.1Gy Testes Temporary Sterility
3.5 – 6 Gy Testes Permanent Sterility
1.5-2.0Gy Ovaries Temporary Sterility
2.5-6.0Gy Ovaries Permanent Sterility
0.5Gy Eye Cataract (After few years)
6.0Gy Skin Permanent Epilation
10-15Gy Skin Death of Tissue
Somatic effects due to acute whole body exposures due to Low LET
When compared to whole body exposure, partial body exposure will not
be life threatening , however it can produce certain serious local effects
These local effects are depends on dose rate and period of exposure
All the early somatic effects do have a threshold dose limit.
26. Late Effects:
Exposed to low levels of radiation over
a prolonged period may lead to late
effects
These effects may found in all organs
Late radiation effects are irreversible
and progressive with increasing severity
occurring with longer follow up times
Progression rate is depends on dose
and dose rate
Ex: Tolerance dose for eye are reported
in the range of 4-5Gy for fractionated
exposure but 1Gy for single exposure
27. Hereditary Effects:
Consequence of mutations induced in germ cells due to exposures
results adverse health effects in the descendants
To estimate the risk of radiation induced hereditary diseases in the
human, two quantities are required:
1. Base line Mutation rate for human
2. Doubling dose- the dose required to double the spontaneous
mutation rate
Hereditary consequences of a given dose can be reduced greatly if a
time interval is allowed between irradiation and conception
ICRP estimates that the hereditary risk of radiation is about 0.2%/Sv
in general public and 0.1%/Sv for workers
28. Deterministic Effects:
Deterministic effects due to the killing/ malfunction of cells following
higher doses
All these effects will definitely appear in the exposed individual, if
person exposed to threshold doses
Severity of symptoms with doses
Can completely avoided by limiting the
dose well below the threshold levels
Ex: All whole Body Syndromes
Partial Body effects
dose
Severity of
effect
threshold
29. Stochastic Effects:
These are statistical in nature
Any dose, however small, is effective for a certain level of risk for
induction of these effects
The risk increases as the dose increases
As such no threshold dose for these effects
Risk of occurrence can’t be completely avoided but can minimized to
an acceptable level
Ex: Cancer , Hereditary effects
But, the human beings exposed in high background radiation areas to
doses 3 - 4 times higher than the average occupational exposure, do
not show statistically significant increase in the incidence of cancer or
heritable genetic disorders
30. Radiation Effects on Embryo & Fetus:
The principal factors are the dose, dose rate and stage of gestation at
which the dose is delivered
Total developmental period of embryo & fetus in uterus is divided
into 3 stages:
Pre-implantation :
1. Time b/w fertilization to attachment of embryo to uterus wall
(0 to 8 days)
2. Most sensitive stage
3. Effect is termed as All-or-Nothing
4. 0.1Gy is also may cause lethality
31. Radiation Effects on Embryo & Fetus:
Organogenesis :
1. Major organs developing stage (9 to 60 days)
2. Exposure during early organogenesis exhibits greatest
intrauterine growth retardation (more radio sensitive cells)
3. A dose of order of 3.5 to 4Gy seems great enough to cause a
miscarriage in most cases
4. 300mSv is threshold exposure limit of mental retardation in this
stage
32. Radiation Effects on Embryo & Fetus:
Fetal Period :
1. Growth of the structures (60 to 270 days)
2. A variety of effects have been documented after exposure
3. Higher doses of radiation required to lethality during this period
than earlier stages
4. Permanent growth retardation observed
In Japanese survivors, irradiation of utero results small head size,
mental retardation etc.,
Finally to be safer side, it must be assumed that the entire period of
gestation from 10 days to 25weeks is sensitive to induction of
malformations by radiation
34. Application Occupational Exposure Dose limit
Whole body
Effective Dose
20 mSv/year
(averaged over defined period of 5 years,
with not more than 50 mSv in single year)
In INDIA, this provision is limited to 30 mSv
should not exceed in any single year
Parts of Body: Equivalent Dose
Lens of Eye 150 mSv/year
Skin
500 mSv/year
(Averaged over areas of no more than any 1 cm2
regardless of the area exposed and nominal depth is
7.0mg/cm2)
Head & Feet 500 mSv/year
(Averaged over areas of the skin not exceeding 100 cm2)
Occupational Exposures
35. Application Public Exposure Dose limit
Whole body
Effective Dose
1 mSv/year
(averaged over defined period of 5 years,
with not more than 5 mSv in single year)
Parts of Body: Equivalent Dose
Lens of Eye 15 mSv/year
Skin
50 mSv/year
(Averaged over areas of no more than any 1 cm2 regardless
of the area exposed and nominal depth is 7.0mg/cm2)
Head & Feet 50 mSv/year
(Averaged over areas of the skin not exceeding 100 cm2)
Public Exposures