Hello friends, today we are looking to finish
the tenth module of our course, where we
are talking about the biological effect of
radiation.
You definitely have gone through the
first lecture by now and actually I am having
a quite a bit of gap between the time I
record to the previous lecture and this one
has I was down a bit with fever and cough
and
cold.
And even today also my voice is quite a bit
restricted, hopefully I can go through.
Just to have a recap of what we have done
in the previous lecture, first you are
introduced to the different units of radiation
doses that we generally use like.
Just to
associate with radioactivity, you are very
early we are associate you were introduced
to
the units like Curie, Becquerel which are
associated with the radioactive disintegration.
But when we are talking about the biological
effects of radiation we have to look for new
units and their units like Roentgen, rad and
rem that came into picture which are
conversion in one of the three R's of radiation
or the SI versions of them gray and
Sievert.
So, you are introduced to those.
And also, several associated factors like
different tissues respond differently to radiation
accordingly we use some kind of tissue weighing
factor these are introduced.
Then you
are introduced the concept of linear energy
transfer, which is actually some kind of
potential or stopping power of a tissue against
radiation.
Or against a, as different tissues
respond differently or the same tissue I can
say respond differently to different particle
depending on their mass and energy level which
is given measurement above in terms of
the LET.
Then you have to you are introduced to different
sources of radiation, living being can
receive radiation from infinite number of
sources like we can, we are always subjected
to
some kind of so-called background radiation
which involves the cosmic radiations and
the rays coming from the outside atmosphere.
Also, there can be radioactive particle
there are going interior to our body or inside
our body through the foods that you are
taking.
There can be particles which are going with
air during the inhalation process.
And also, nowadays with increase in the medical
equipments, there are significant
fraction of radiation being contributed by
different kind of medical instruments, like
where instruments like MRI which does not
require any kind of radiation dose,
introduces any radiation does not introduce
any kind of radiation effect.
Very general or
simple kind of technique like an X-ray can
impose radiation equivalent to 11 days of
natural radiation.
Whereas CT scan which is again a quite common
technology nowadays
that just one sitting of head CT scan can
lead to radiation exposure to your body which
is
equivalent to 365 days that is one full year
of natural radiation or more than 13 days
of
flying.
Of course, when you are flying, or you are
at higher altitude you are exposed to larger
amount of cosmic radiation and that is why
flying also induces quite a bit of radioactive
effect now, in our on our body, but this modern
medical equipments which involves
radiation like-x rays or any kind of scans,
they also can have significant effect and
therefore, we need to be very very careful
before undergo any such kind of them.
Then we have discussed about the biological
effects of radiation and the cellular effect
of
radiation.
You have seen the cellular effects of radiation
can be of two types primarily,
one is the indirect effect which leads to
the particle radical formation as our cell
primarily comprises of cytoplasm and water
is the main component of the cytoplasm.
So,
the radiation generally breaks the H 2 O molecule
there leading to the formation of
several very dangerous kinds of radicals such
as the peroxide, the hydroxyl and also so
called the superoxide's.
They all, can have important effects or important
detrimental
effects on the cell.
And there can be direct effect also whether
radiation can change the
demorphidology or the morphology of the DNA
itself we shall be looking more into
them in today's lecture.
Now, the terms for introducing in a last lecture
itself, but let us look a bit more into this
two terminologies that is whatever the biological
effects radiation may have they are
generally classified into two categories,
one is stochastic, and other deterministic
or
sometimes called the non-stochastic effect.
The deterministic effect generally refers
to
those kind of phenomenon where or which appears
only once a threshold dose of
radiation is based that is if the radiation
exposure is less than the threshold, then
you will
not find any kind of effect or only when the
threshold is reached the effect becomes
prominent.
But once you have reached the threshold increasing
the dose beyond that keeps
worsening the effect.
So, the behavior can be, means if we plot
something like this,
where effect on this side and the dose on
this side, till if this is a threshold then
below
this threshold you will not find any kind
of effect, but above the threshold effect
keep
some increasing very, very sharply.
So, this is what we called the deterministic
effect.
Deterministic effects generally are immediate
effects or short-term effects.
Once the threshold is reached they are guaranteed
to appear.
And also, the threshold
value actually depends upon the particular
person or particular place which is subjected
to radiation because different person or in
fact, the different tissues of the same person
have different values for this threshold.
And also, which kind of effect is going to
appear
accordingly the threshold is also going to
vary.
And any early effect as I have mentioned
and most of the normal tissue late effects
are deterministic or non-stochastic in nature.
These are some typical values of the threshold
corresponding to the deterministic effect.
Like generally the genital organs are the
most affected by the radiation.
And as you can
see here when they are subjected to say the
testis is subjected to a single absorption
dose
of strength 3.5 to 6 Sievert Sv then that
is actually quite high dose or a prolonged
absorption of measuring to 2 Sv-year then
that will lead to a permanent infertility.
Ovaries even more sensitive generally the
female genitalia is much more sensitive to
the
male genitalia that is why the value is even
smaller, even 10 times smaller to this.
The lens of eye that is also very very sensitive
to this when it is subjected to a radiation
dose of something like 0.5 to 2 Sievert only,
it can result to a milky of lens.
Cataract may
appear with a dose of 5 Sievert or greater
than 0.15 Sievert-year for prolongment
radiation dose.
And bone marrow probably is the most sensitive
kind of tissue or
sensitive kind of part of the body related
to radiation effects with a very relatively
smaller radiation dose of only 0.5 Sievert
it can lead to the blood forming deficiency.
So, and also this data are quite a bit old,
but still very much valid.
These are
recommendation given by the well known ICRP
that is International Commission on
Radiological Protections who generally says
the standard for any kind of radiation-based
guidelines.
Now, putting this in comparison with stochastic
effect, for stochastic effect
there is no such threshold dose.
So, stochastic effect whether that will appear
or not that
does not depend upon the magnitude of the
radiation that the object is being subjected
to.
Rather there more likely with increase in
the dose.
Or I can say that the severity of the
stochastic effect does not depend upon the
intensity of the dose, but as the dose
intensifies their appearance is more likely.
So, we cannot say that for this particular
dose, this kind of stochastic effect is going
to
appear or not.
But of course, they are more likely.
And also, there is no dose; however,
stochastic effect starting to occur, they
may not at all appear, but also they can appear
with quite a small dose, because generally
the effect is cumulative when someone is
subject to a quite small dose for a very prolonged
period, then the stochastic effect can
appear.
But I repeat if the strength of the dose is
more, then they are more likely to appear,
but
the severity of the diseases severity of the
effect is has no relation with the strength
of the
dose.
And stochastic effect actually concerns much
larger or more catastrophically
affects of radiations such as the carcinogenesis
and also the gene defects or DNA
mutations leading to hereditary effects.
So, stochastic effects are long term effects,
and
they are also quite difficult to spot, whereas
deterministic or non-stochastic effects are
immediate effects and they appear once their
threshold is breached.
Now we need to get some idea about the human
cell cycle.
Each human cell undergoes
quite a few difference stages of development.
The first stage of importance is the G 1
stage like shown in the diagram they are principally
four or five stages.
Once the first
stage is the G 1 phase, which is the growth
phase or growth phase one during the cell
grows.
And at the end of G 1 phase, it is ready to
replicate the DNA, then is the S phase
when the DNA replication happens.
Then because to the G 2 phase where the DNA
replication is already done, so they makes
further growth and ensures that it is ready
for
cell division and then the most important
one the mitosis during which the cell divides
into two.
And cytokinesis actually is a follow up step
of mitosis sometimes called a part of the
mitosis itself.
And some cells may have an intermediate G
naught stage as well, where
many human body cells may exit the cell cycle
remain in a resting position or some kind
of neutral position for some time in fact
some cells may remain there for a very, very
long time and that is referred to as a G naught
phase.
Now, scientist have done some experiments
to understand which particular phase of this
human cell cycle is most vulnerable to radiations.
And to facilitate that what they have
done they have chosen different cell samples
and applying some kind of sophisticated
techniques, they have ensured that their cell
cycles are exactly following the same
timings that is they are perfectly synchronous
with each other.
Once they have developed
quite a few cell colonies which are perfectly
synchronous with each other then different
cell colonies were subjected to different
amounts of radiation and also in different
phases
of their individual cell cycles.
And it has been observed that a cell is the
most vulnerable to radiation when that is
going
to the mitosis process or about to go through
the mitosis process.
When we subjected to
radiation in the other phases like G 1 phase
or S phase or early part of G 2 phase, effect
of radiation is quite small, but when it is
going to the mitosis then only it is most
vulnerable, or it is about to start the mitosis
somewhere here then also it is very much
vulnerable.
And there is a reason also.
Like we know that inside the cell there are
different kinds of components.
Now, if
radiation effects some of the components,
say if it effects a mitochondria, the
mitochondria may get permanently damaged,
but inside a cell there can be several
mitochondrion and therefore, just damaging
one may not affect the cell performance too
much, but once the radiation effects the nucleus
then the radiation is definitely going to
be the very important and the cell is going
to suffer, because nucleus is a main part
of the
cell and that is unique.
And the nucleus is in the most vulnerable
position when it is going to the mitosis.
This is
a very rough schematic representation of cell
division where both mitosis and meiosis are
shown.
Meiosis is a one during which the chromosomal
exchanges happens, but that is
not of our interest.
Let us focus on mitosis only.
There are principally four different
phases, prophase, metaphase, anaphase and
telophase, and sometimes also fifth follow
phases cytokinesis which is more like a post
processing phase.
During the prophase phase the chromosomes
are duplicated this is where the
chromosomes are duplicated.
So, initially if there are if there are n
pairs of chromosomes
like this is a parent cell where there are
in this diagram, there are four chromosomes.
The
chromosomes are initially duplicated in the
prophase phase leading to four
chromosomes.
And now our four pairs of chromosomes I should
say.
And then this chromosomes align each other
along the metaphase plane during the
metaphase process, and then they subsequently
separate out to develop to new daughter
cells during the anaphase getting completed
during the telophase process.
Accordingly,
we get two different daughter cells which
are identical to the parent cell.
Mitosis is the
most common type of cell division that we
can see and that is the one that is responsible
for development of our body from a single
cell embryo to a fully-grown human person
human body.
So, if mitosis is affected by radiation then
there can be real catastrophic effect, and
something known as cell killing.
Cell killing refers to reproductive rate of
a certain
fraction of cell colonies when subjected to
acute radiation.
Like when a cell is affected
by radiation, then the cell may lose its reproductive
power, and accordingly it is
terminology wise it is called the cell is
being killed, that is cell killing or causing
the
reproductive death that depends and upon the
level of the dose.
Again, experiments are
conducted with different cell colonies, being
subjecting them to different levels of
radiation, and then observing what fraction
of that has suffered this cell killing.
And it
has been found to be proportional to the LET
again.
Like in case of high LET radiation it is a
very, very short decline.
You can see it is a
vertical straight line which is going down
very, very rapidly.
Here one thing of
importance here is a vertical scale is a logarithmic
scale and so the change is extremely
rapid.
Whereas for low LET radiation, the change
is very small particular in this part,
there is very little change, it is increasing
only later on.
So, for a high LET radiation
dose, the effect of for radiation causing
the cell killing is very, very prominent.
And now this cell killing can be of five different
types which are shown here.
A cell
when subjected to radiation can follow different
kinds of routes, all associated with
several kinds of enzymes and chemical processes.
One thing you have to remember here
is that the while we are talking about the
effect of radiation on cell killing, actually
all
the effects are more or less chemical in nature
particular the indirect effect of radiation.
Because a cell compresses a several kinds
of chemicals and as we have already seen the
indirect effect of radiation is to develop
free radicals.
And once the radicals are
developed then the next part is just chemistry.
So, from that point of view, the effect after
that pre radical formation has taken place
is the same as with any kind of chemical
poisoning.
So, the way the cell is going to react to
a nuclear accident, and the way it is going
to
react to some chemical accident, there may
not be too much different.
But of course, the
fact is that for a nuclear accident, the affect
may be very, very prolonged because the
radioactivity may remain in the surrounding
for a few hundred years as well.
So, these
are the five different kinds of mechanisms
of cell may undergoes apoptosis, necrosis,
senescence, autophagy and mitotic catastrophe.
Apoptosis is a highly regulated mechanism
of cell death.
Distinct cytoplasmic and
nuclear morphological changes are recognizable
in cells undergoing apoptosis, such as
shrinkage of the cell, contraction and membrane
blebbing, nuclear condensation,
fragmentation of the DNAs, and also cell destruction
into membrane-bound particles.
So, apoptosis is the most common type of cell
killing process in fact, a body to replace
the old cell by the new one also follows apoptosis,
apoptosis.
But apoptosis is the first
most prominent kind of effect cell killing
mechanism that radiation can lead to.
Then
there is necrosis, necrosis is generally is
considered as a tumor cell death process that
predominates after a high radiation dose treatment.
While at a lower dose, it has been
indicated as a passive and unregulated event.
One thing we have to understand here the
all the effect of radiation may not be bad
because treatment of carcinogenesis such kind
of things also you makes use of high dose
radiations.
And there the objective radiation is
to kill the affected tumor cells.
So, necrosis general is a primary mechanism
where which
leads to the cell killing.
Then senescence is a known strategy during
aging and increase of senescent cells in
older tissues or in radiation treated tissues
maybe responsible for some pathological
onset.
Radiation may induce accelerated cellular
senescence, a state of irreversible
growth arrest in which the damage cell show
altered functions and despite being vital
are
no longer competent for proliferation.
So, cell is not able to grow any further and
also
not able to divide any further.
It has been demonstrated that senescence is
the principal
response of some cell types at lower radiation
doses, whereas at higher doses they may
lead to apoptosis or in certain cases necrosis.
So, this tells the primary types of cell killing
mechanism that you can find when that is
subjected to radiation, apoptosis is the most
common one, necrosis can also be found, but
when the radiation dose is low then the most
common one that you will find is this
senescence.
But when the dose is high it is more likely
to be apoptosis or in certain cases
necrosis.
Autophagy is basic catabolic mechanism that
involves cell degradation of unnecessary or
dysfunctional cell components.
Again, it is a very natural process, the dysfunctional
cell
components are being eaten up by the cell
itself or some other part of the body whose
function is to clean the unnecessary portions,
thereby cleaning the body itself.
It has been
described as an adaptive response to survival,
whereas in other cases it appears to
promote programmed cell death via non apoptotic
mechanism.
And finally, MC or metabolic catastrophe;
it is described as cell death mechanism
occurring during or after aberrant mitosis
associated with various morphological and
biochemical changes following radiation-induced
incomplete DNA synthesis.
It can also
be caused by chemical or physical stresses
and represents and oncosuppressive
mechanism to avoid genomic instability.
It has been defined as a special example of
apoptosis because it shows several biochemical
features which are quite similar to
apoptosis only.
Now, as we have repeatedly mentioning that
the way different tissues respond to
radiation are not same.
Of course, when a cell is subjected to radiation
particularly when
is about to go mitosis that is very much likely
to go for cell killing, that is reproductive
death.
However, that likelihood that is individual
to the tissue itself.
Based upon the radio sensitivity tissues can
be defined in to or divide into three
categories highly radiosensitive, moderately
radiosensitive and least radiosensitive.
Highly radio sensitives are those which generally
are very important tissues of the body
and they are also affected strongly by the
radiation.
The most important one of them
maybe bone marrow.
This is a picture of bone marrow being suffered
by radiation.
The
lymphoid tissue can be there.
The gastro intestinal epithelium is also very
important
which actually forms the inner layer of our
GI tract, those cells are very, very active
and
they are going to continuous mitosis process.
So, they are very likely to get affected by
radiations.
The gonads I kept on mentioning repeatedly
there also very much affected by
radiation, even small amount of radiation
also can also lead to permanent infertility
for
both male and female.
The embryonic tissue that is the fetus that
is also highly sensitive
to radiation.
The under moderately radiosensitive tissues,
you can get skin.
Skin is always subject to
radiation particular the background radiation
or cosmic radiation.
It is being subjected to
the effect of radiation on skin can be in
the form of, radiation is of the skin appearance
small pimple kind of structures or rashes
etcetera.
And can be even more severe
depending upon what level of radiation it
is being subjected to.
This is a picture where
you can clearly see here there are lots of
disintegrations of the internal cells and
in this
part as well because of the effect of radiation
they are strongly affected.
The vascular
endothelium, lung, kidney, liver and also
the lens of our eyes, they can also be strongly
affected by radiation.
But the parts which are very less affected
for most of the normal radiation doses there
almost immune to radiation can be the nervous
system, thankfully on nervous system is
hardly affected by radiation, and therefore,
therefore, even when someone is subjected
to
radiation for a prolonged duration of time,
his nervous system keeps on working
properly.
The muscles, the heart tissues like muscles,
and bones, and cartilage and
several connecting tissues there also very
less affected by radiations.
This is a set up pictures which shows the
effect of radiation on some highly sensitive
tissues.
This one is the normal picture of a bone marrow;
it is not subjected to radiation.
It is subjected to radiation dose of 8 gray,
you can see there are very less number of
cells
appearing.
And the when you subjected to higher radiation
dose of 14 gray, the complete
structure has changed.
And accordingly, most of the bone marrows
have suffered the cell
killing or reproductive death not being able
to cause develop newer blood cells, and
therefore may lead to the formulate to leukemia.
Small intestine, if it is macroscopic view
then you can see with 8 gray of this the muscles
are corresponding to tissues are elongated,
when only subjected to a 14 gray dose then
this cells have already died, this tissues
rather, they have already died and severely
affected.
And if you take a microscope view of the same
thing, then you can see with 8
gray dose, they have already started to get
affected.
Their shape has got distorted and
also some of them some discontinuities have
started to appear in this zones, they have
started to get separated from the base.
And when it is much higher dose of radiation,
they
are completely separated from the base, and
their shape is also extremely different from
what we initially had.
So, these are the effects radiation may have
on highly sensitive
tissues.
And radiation can have even severe effects
on the fetus or embryo.
Particularly during
the first eight weeks of pregnancy.
You can see within first two weeks if it is
subjected to
a dose or threshold dose of 50 to 100 milli-gray
then it can lead to the death of the fetus.
Whereas, within 2 to 8 weeks, with the threshold
dose of 200 or 250 milli-gray, it can
lead to congenital anomalies, growth retardation
and childhood leukemia.
For later part
the chances are much lesser, threshold also
keeps increasing, but there the effect of
radiation primarily not fetus death, but severe
effects on the mental part, that is it can
lead to mental retardation, it can lead to
intellectual deficit or in severe mental
retardation may also appear in very in the
later part of pregnancy.
And that is one primary reason that nowadays
pregnant ladies are not suggested to go for
x-rays.
Earlier x ray was the most common mechanism
that was used by the doctors to
test the status of the fetus, but nowadays
everyone is asked to go for ultrasound, because
it is almost the use of x rays almost banned
for pregnant ladies that is precisely to avoid
these effects of radiation.
Of course, ultrasound does not involve any
kind of radiation
effects as that is a sound wave based techniques
and hence that is completely that can
completely avoid any of this kind of effects.
Then we come to the genetic effects of radiation.
It should be genetic effect of radiation
not radioactive.
Now, that is where you are talking about the
direct effect.
Direct effect
refers to when the DNA structure is directly
being subjected to incoming radiation
something like an UV photon or an IR photon.
Again, that is very likely to appear during
the mitosis process itself, because during
others stages of the cell division or cell
cycle I
should say the DNA is not exposed, the DNA
is kept inside the nucleus and it has very
less chance to get exposed to the radiation.
But during the cell division process the
DNAs are open and that's why the DNAs make
get subjected to radiation.
And there can
be several kinds of effects of radiation,
and the primary effect may can be the causing
the
nutrition to the DNAs thereby completely changing
the characteristic of the offspring
who are going to come from the same from that
person.
If the jam cells are subjective to such kind
of radiation, generally they lose the power
to
reproduce, but if any of those jam cells which
are affected by radiation, they are able to
survive and then lead to the formation of
a zygote, then there is a high chance that
the
next generation will be affected by radiation.
There can be several kinds of effect that
we
can find very commonly the down syndrome is
one of the effects, we can have chronic
myelogenous leukemia, or we can have also
cystic fibrosis, we can have hemophilia.
And we have essential hypertension.
These are all different kinds of effects that
may
come because of radiation.
Again, these effects are also similar to any
other kind of genetic effects like we have
mentioned in case of indirect effect, the
effect of radiation is to, is to cause the
radical
formation and then rest part is similar to
any kind of chemical effect.
Similarly, here also
here radiation is causing a mutation to the
DNA or causing a changing in the structure
of
the DNA, and then next part is similar to
any kind of genetic defect, genetic defects
I
should say.
So, there are several models of gene theory
that are available which tries to predict
this,
but still very less is known and also this
genetic effects of radiation are more stochastic
type that is they are long term effect, it
is very difficult to understand whether they
are
going to appear or not, very difficult to
understand immediately whether they are going
to appear or not.
Only with a observing over a prolong period
time, we shall be able to
make ensure that they are going to appear.
Particularly if the effects comes in the next
generation then that is quite difficult to
correlate, because the defect can the effect
or
genetic nutrition that is getting caused that
can be from any of the parents, can be from
the father, can be from the mother and how
much effect is getting transferred that is
also
quite difficult to practice difficult to predict.
So, this takes us towards the end of this
particular module, actually there are several
other factors that could have been added here,
and the length of the module itself is also
quite short.
But any further discussion that I would like
to have about the effects of
radiation, it can have on human cells or on
the DNA that requires the much more
knowledge about the biology and also genetics
which I am I am not at all conversant
with.
And also, that is not relevant to understand
from the point of view of this course
that is why you are keeping this module quite
short.
Now, just to summarize the key points from
this particular module; here your interest
to
specialized units for measurement of radiation
exposure and doses units like Sievert and
gray.
Then living being can get exposed to radiation
to several means.
Role of medical
diagnostic tools is increasingly dominant
in worldwide population dose, particularly
in
technically-advanced countries like we have
seen in 1980s where medical instruments
are contributing only a paltry portion in
total immunity doses.
In early 2000s, it is all
contributing nearly half of the total radiation
dose in United States alone.
Different human tissues respond differently
with radiation, with the bone marrow and
gonads being the most sensitive ones.
And also, I should mention about the fetus.
Indirect effect of radiation is the production
of free radicals inside the cell and
subsequent chemical effects.
Direct affect can be the mutation of DNAs
leading to
numerous genetic diseases.
Deterministic effect of radiation is effective
beyond a
threshold dose, but once the threshold is
breached, then the severity of the effect
is
directly proportional to the dose itself.
Whereas, the stochastic effect has no threshold,
it
may appear, may not appear it is very difficult
to predict, but larger the strength of the
dose, the more likely are this stochastic
effect appearance, of this stochastic effects,
so
that is all for this tenth module.
This probably is the shortest possible module
that we have in this entire course because
most part of the relevant discussions are
related to biology and medical sciences which
I
have tried to avoid in this.
But something that I could have could have
added rather that
is whatever we have discussed here are the
bad effects of the radiation, but there can
be
several good effects also, the use of radiation
in cancer treatments or similar kind of
other fix again some medical terminologies
and medical knowledge is required.
So, I
have not gone there.
And finally, that something that I must have
included that is how can we get how can we
get protected can get ourselves protected
from this radiation.
Particularly from the very
beginning of the course we repeatedly saying
that whenever there is any discussion of
setting up a nuclear power stations, the major
discussion is to protect the surroundings
from the dose of radiation, but whether that
is at all important or what kind of protection
we should have in a nuclear power stations
but that discussions I have not put in this,
because that will be the topic of our next
week where we are going to discuss about the
safety and security of a nuclear power plant
and there we shall we starting to, starting
with the discussion of how we can get ourselves
protected from radiation itself.
So, thanks to all of you for listening.
If you have any query please write to us we
are
shall be happy to answer you.
Thanks a lot.
Bye.
