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So let's examine from the radiation effects at the tissue level.

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What happen is the interaction of radiation in tissues can be understood as the

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following. Energy is deposited randomly and very rapidly,

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typically of the scale of 10 to the power of -10 seconds.

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Any radiation interaction, the energy is deposited randomly.

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That can be via excitation, ionization, and also thermal heating.

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While thermal heating, it is large radiation, but these are the three different

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ways the energy from the radiation can deposit in the tissues.

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The radiation interactions are grouped into two broad categories.

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One is called the direct interaction, the second one is called indirect reactions.

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What is direct action? The direct action is when radiation interact

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directly with biological macromolecules such as DNA, RNA, or

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protein, and we call that as direct action.

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The chances of happening the direct action is very small because the biological

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macromolecules are so small. On the other hand, the more obvious one or the

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more probabilistic interaction is indirect action.

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The indirect action can be understood as following.

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The radiation interaction within the cell medium, which creates

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reactive chemical species, which in turn interact with target molecule.

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So they are a two-step process. Example is creation of free radicals due to

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radiolysis of the water. And because of that, the free radicals in turn interact

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with the biological macromolecules causing biological damages.

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So that is the just understanding at the tissue level.

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So in general, how does ionizing radiation damage DNA?

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This particular slide showing different images, basically showing on the left-hand

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side, the cartoonish drawing of a radiation interaction with the water molecules.

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And in a direct reaction, what happen is like any water molecule, if it interacts,

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it releases electron that can directly hit the DNA, and that can cause a

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direct damage to the DNA. The bottom left, it shows the DNA strands,

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and it can either have indirect or directly causing some of these

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free radical damage, a single strand or a double strand.

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And a lot of the time, it repair itself and you don't see the effect, which is a

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really good thing. On the other hand, these electron, which is a path of the

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electron on the right-hand side top figure shows they are moving around in the cell

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medium, causing water molecule to break.

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And the water molecule, the hydroxyl, which is now free radical, can damage DNA

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molecule at both the strand, and either it repair itself or it can cut off and

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break away. When it happen, that's when it leads to other manifestation.

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This is at the tissue level to understand what happen at tissue level.

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Again, I'm not talking about the magnitude of radiation, I'm just telling

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interaction of the radiation with matter.

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Now, the indirect action, let's spend more time on this one because that is the

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one, the highly probable way of interaction compared to direct action.

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The free radical do not typically produce significant biological damage because

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they have a very short period of time, 10 to the power of minus 10 second.

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However, these free radical recombining, combine forming hydrogen

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peroxide, which is a cellular poison, and OH star radical,

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which is a toxic substance. So these two floating in the cell media or the tissue

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media, they are both highly reactive and can produce biological damage.

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And that is the understanding we have about indirect action.

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So on the left-hand side is a flow diagram of the interaction of ionizing

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radiation with the water molecules in the tissue and what happen.

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So if you look in here on the left-hand side is the timescale given at the time of

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interaction, ionizing radiation interaction at the time 0 seconds.

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And then if we go through the left and go down the scale, there is always physical

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stage where the water molecules breaks up, either because of the excitation,

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the remaining water molecule become H2O star.

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Excitation means the electrons are excited to the higher energy level, or it

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cause ionization, means it can knock off an electron from the water molecule, where

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the free electron will be going around and the remaining water molecule is H2O

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plus. This is the physical stage, and this timescale is about 10 to the power of

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-15 second.

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Once this occurs, the next stage, which is a physicochemical stage you see here,

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is either the hydrogen, the water molecule which is excited, can break up causing

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this H+ and HO star, or it can also produce the other

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way, which is H2 and 2HO. Or all these things can happen.

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The bottom one at the chemical stage, you see all these free radicals are created,

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all these molecules are created, which

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have a unique way of interacting with the DNA.

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So the most important water radiolysis reactive species-- When I say

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radiolysis, it's the breaking of the water molecule.

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So the most important water radiolysis reactive species are hydroxyl

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radicals, which are produced here all the way down, and hydrated electron, which is

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a free radical electron going around.

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These reactive species can interact with DNA if they are

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produced in the close proximity of the DNA.

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So that is a condition, if it has to be produced within close proximity of the DNA,

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you're talking about less than 10 nanometer.

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That's one of the reason why most of the radiation interaction, we don't see the

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effect because the body either absorbing or entirely repelling and all those

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things. When it happens, and when it's very close to the DNA molecules and so

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forth, then these things, the tissue interactions can occur.

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Let's capture that in understanding the radiation interaction and energy deposition

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on different stages, what happen in different stages and what timescale.

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I just draw here the border for physical stage, where the radiation interaction

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with atoms and energy transfer, which is occur, ionization or excitation, the

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chance of thermal interaction is much less, and that usually occurs in the 10 to

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the power of -16 second. The physicochemical and chemical interaction, that is

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where the energy is deposited into the tissues, can create in the formation of

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initial radicals and low-energy electrons, or in a reaction of reactive

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species with molecules of recombination.

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That's usually of the order of 10 to the power of -12 second to 10 to the power of

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-3 second. Again, microsecond to nanosecond to picoseconds.

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The biochemical interaction, which is the modification of the biomolecule, example,

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DNA damage, such as base damage or double-strand break, all can occur in the

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timescale of one second. The biological effect, the cell or tissue response to

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biomolecular modification can occur from seconds to decades and so forth.

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That is the general understanding we have of the radiation interaction at the

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tissue level.