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Transcript of 6/10/14 Rad Bio: interactions with matter p. 1 of 85 Illinois Institute of Technology PHYS 561...
6/10/14 Rad Bio: interactions with matter p. 1 of 85
Illinois Institute of Technology
PHYS 561 RADIATION BIOPHYSICS:
Lecture 3:Interaction of Photons with Matter;
Radiation Chemistry;Introduction to BiologyANDREW HOWARD
10 June 2014
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Radiation interacts with matter
We’ll investigate the chemical changes that occur in matter, particularly soft tissue, when ionizing radiation impinges on it;
But first we need to finish discussing the initial interactions themselves.
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Outline of Session
Left over from chapter 5:– Pair production– Bremsstrahlung– Charged particles &
matter– Interaction of photons
with matter– Size scales and
biological cells– Energy deposition at
different physical scales– Neutrons
Chapter 6:– Types of energy
transfer from electrons– Free Radicals– Radiation Chemistry of
water– Fricke dosimeter– Recombination,
Restitution, Repair
Biology 101
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Relevant references Some significant references on photoelectric effect and
the interactions of photons with biological tissue:
1. J.H. Hubbell (1977) Radiation Research 70: 58-81. 2. J.H. Scofield (1973) Theoretical Photoionization
Cross Sections from 1 to 1500 keV, Report UCRL-51326, University of California Lawrence Livermore National Laboratory, National Technical Information Center, Springfield, VA
3. A.M. Kellerer and H.H. Rossi (1971) Radiation Research 47: 15-34
4. H.H. Rossi (1959) Radiation Research 10: 522-531
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Typos of the Day
Page 79, first paragraph under “IMPORTANCE OF THE COMPTON PROCESS”, 4th line:“with attention the the” “with attention to the”
Page 86, List of possibilities, #3:“Either M or m0 is at rest” “Both M and m0 are at rest”
Page 87, 2nd paragraph, 1st line:“The four principle” “The four principal”
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Pair Production
e- + e+; see fig. 4.7 Can happen if E > 1.022 MeV = 2 * m0(e-)c2
Rapidly increasing cross-section > 1.022 MeV This is the predominant mode of interaction over a
range from a bit above that value up to ~5MeV Stopping power/atom varies as Z2
Energy transferred is h - 1.022 MeV
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What pair production does
Scattering nucleus plays fairly passive role– not much momentum transferred to nucleus– but it does soak up some momentum;
otherwise we couldn’t get it to happen at all Generally the positron gets annihilated, giving off a
pair of 0.511 MeV photons. These generally escape and are not part of the absorbed energy
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Bremsstrahlung:Radiative Energy Loss
“Braking radiation”:A fast electron loses energy to its environment in a nonspecific way due to Coulombic interaction with neighboring charged particles.
The static particles are much more massive than the electron, so they don’t get accelerated nearly as much as the electron does: but the electron does get accelerated.
What happens when an electron is accelerated? It has to radiate! This type of Coulombically-motivated radiation is Bremsstrahlung
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Dependence of Bremsstrahlung on Z High-Z elements have much higher
cross sections for braking radiation for a given initial electron energy because the acceleration goes like Z
Higher electron energies produce more Bremsstrahlung than lower electron energies
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Significance of Bremsstrahlung
Example in X-ray generators: 1.5418Å (8KeV) characteristic X-rays are produced
in great quantity when we shoot fast electrons at a copper target: L-to-K shell transition emissions
BUT: we also get a lot of radiative transfer of energy from the electrons as they move past the copper atoms. This gives rise to Bremsstrahlung, which has no characteristic energies.
Thus the spectrum is like this:
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Output X-ray Spectrum of a Copper Target
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Overview of photon-medium interactions
We’ve seen four mechanisms by which photons can transfer energy to a medium:
Photoelectric effect (mostly below 1MeV) Coherent scattering (mostly below 20 keV) Compton scattering (peaks around 1MeV) Pair production (starts @ 1.022 MeV; dominates at
high energy) We can write the overall event cross-section as
µtot = PE + coh + Compton +pair
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What predominates where?
Cf. fig. 5.2(a),(b) For lead, Compton falls off from 100 keV
upward and pair production takes over ~ 5MeV
These figures make the distinction between absorption and transfer as well
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How do mixtures absorb?
We’ll come back to this later: Mixtures, including polyatomic
compounds, absorb according to their individual atomic attenuation properties, weighted by their mole fraction
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Attenuation Coefficients for Molecules (and mixtures)
Calculate mole fraction fmi for each atom type i in a molecule or mixture:
– subject to ifmi = 1
– That’s why we call these mole fractions
Recognize that, in a molecule, fmi is proportional to the product of the number of atoms of that type in the molecule, ni, and to the atomic weight of that atom, mi:fmi = Qni mi
(Q a constant to be determined)
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Attenuation coefficients, concl’d
Thus ifmi = i Qni mi = 1 so Q = (i ni mi)-1
Then (/) for the compound will be(/)Tot = ifmi (/)i = iQni mi(/)i
= (i ni mi)-1 ini mi(/)i
This will, in fact, work even with mixtures of compounds, as long as you keep your mole fractions straight.
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Calculating Mole Fractions and Attenuation Coefficients
Example 1: Water (in book):– H2: n1 = 2, m1 = 1; O: n2 = 1, m2 = 16– Q = (i ni mi)-1= (2*1 + 1 * 16)-1 = 1/18– Thus fH2
= 2/18, fO = 16/18,
– (/)Tot = ifmi(/)I = (2/18)*(0.1129cm2g-1) + (16/18)(0.0570 cm2g -1)= 0.0632 cm2g-1
Benzene (C6H6):– C6: n1 = 6, m1 = 12; H6: n2 = 6, m2 = 1– Q = (6*12+6*1) = 1/78, fC6
= 72/78, fH6 = 6/78
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Interaction of Charged Particles with Matter
See pages 84 & 85 in the text-Provides solutions to the dynamical equations describing motion of a heavy charged particle past a stationary electron or (by relativity) motion of an electron past a stationary heavy particle: F = kze2/r2 along line MQ
Q
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Interaction of e- With Heavy Charged Particle
Momentum imparted to electronat distance of closest approach:
classical coherentscattering by e-:
non relativistic
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Interaction of Charged Particles with Matter
Recall diagram 5.3, p.84. The crucial equation is for E(b), the energy
imparted to the light particle: E(b) = z2r0
2m0c4M/(b2E)where E is the (nonrelativistic) kinetic energy of the moving particle = (1/2)Mv2.
It increases with decreasing impact parameter b, which stands to reason
Energy imparted is inversely proportional to the kinetic energy E of the incoming heavy particle!
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Why does this formula matter?
Rate of energy loss is inversely proportional to the energy of the incoming particle
So most of the energy is yielded up as the heavy particle approaches its resting state
There are some details we’ve skipped, but they’re readily available in other textbooks.
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Relativity tells us this is important! We usually think about the electron moving and the heavy
nucleus being stationary, not the other way around. Why do we go through this derivation?
(a) This could actually happen as described (b) Galilean (or Einsteinian!) relativity says this is equivalent to
what happens if the electron is moving and the heavy particle is at rest. That’s the more typical situation: but the analysis still works.
(c) If M=m0, i.e. an electron-electron interaction, then the assumption of minimal interactivity fails, but we still find that the energy transfer goes like 1/v2 or like 1/E.
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Final steps in absorption
Let’s think about a high-energy photon entering a biological medium
It undergoes a modest number of scattering events that give rise to energetic (keV - MeV) electrons
These energetic electrons will themselves only affect the medium once they have transferred energy to other electrons in ~10-50 eV packets
Four mechanisms for doing that:(a) Delta rays (c) Bremsstrahlung in motion(b) Photoelectric (d) Direct collision
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Delta rays We expect that each individual event transfers a small amount
of momentum, so the incoming electron doesn’t change direction all that much
There are exceptions: these are delta rays. The “delta ray” is the common name for a secondary electron
that itself has enough energy to ionize other things The ionization events caused by the delta ray can produce
electrons that have energies up to half of that of the primary electron
So some delta rays will even produce tertiary electrons that are themselves delta rays!
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Photoelectric processes
If the primary photon is absorbed by an atom, a K or L-shell atomic electron is ejected
This makes an outer-shell electron hop in to fill the inner-shell vacancy, giving rise to an output photon with an energy equal to the difference in shell energies
The photon has to undergo ordinary scattering (probably Compton) in order to transfer energy
This process is most likely in high-Z media, for which the capture cross section is measurable
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Bremsstrahlung with movement Caused by Coulombic interaction of an emitted
electron with nucleus Incoming electron decelerates a little due to these
interactions This is not like the 1/E-dependent process we just
described, because not much happens to the target in this instance
Loss due to Bremsstrahlung is important for incoming electrons above 10MeV in lead or 100 MeV in water: that corresponds to almost 200 times the rest energy of the electron
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Direct collisions Extreme form of
Bremsstrahlung: electron stops and gives up all its kinetic energy to the absorber
Rare but can be measured
e-
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Dose: a definitional reminder
Remember that dose is about deposition (or absorption) of energy per unit mass, while kerma is about transfer of energy per unit mass
So energy that escapes the neighborhood of the initial event may not count in the dose in that region, but rather will count in the dose of some other region
Kerma, by contrast happens at the moment of impact
So kerma can be lower or higher than dose depending on circumstances
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Dose and KermaSee Fig. 5.5 in text.
Because secondary events extend farther into tissue (or other) than the initial deposited radiation, dose extends farther into the interior than kerma.
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Photons interacting with matter
We mentioned at the beginning of the lecture that the interaction of a high-energy photon with a chunk of matter involves
– Photoelectric effect– Coherent scatter– Compton scatter– Pair production
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Compton Scattering, Revisited
The most important of these processes for h > 100 KeV is Compton scatter, especially if the matter is water or tissue
See fig. 5.2(B) in the text to see why:µab/ (Compton) predominates above 100KeV
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Compton Processes in Tissue
Biological soft tissue is predominantly made up of H, C, N, O, and a little P and S. So attenuation of photons is dominated by those light elements (Z 16)
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Dose
Remember Dose = energy deposited per unit mass.
What is the meaningful size scale for a mammalian cell?
We’ll need to know this to estimate dose on a cell.
size scales 5m
1 g/cm3 for water or soft tissue
mass of (5m)3 =(5 * 10-4cm)3 =125 * 10-12cm3 1g/cm3
=125 * 10-12g = 1.25 * 10-13kg
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Energy Absorbed in a Cell
Suppose N Joules of energy are deposited in a 70 kg human. Nominally the dose is N/70 Gy.
How much energy is deposited in a single (5µm)3 cell? (N/70)Gy * 10-13 kg= (N/70)*10-13 J= (1.3*10-15)*N J= [(1.3*10-15)*N]/1.609*10-19 J= 8500*N eV. So it’s a lot of energy!
Is the Bethe-Blocke continuous slowing-down approximation applicable here? No! Too much energy is being stopped per cell for it to be applicable. But we try to use it anyway.
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Track structure
We draw different kinds of conclusions depending on the size range we think about
The smaller the target, the bigger the fluctuations in dose that we have to recognize
So deliver of 1 cGy to a large volume could mean we’re delivering anywhere between 0 and 103 Gy to a single chromatin fiber
We can attempt to account for this in various ways; Rossi does it in terms of EY/d
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Can LET tell us what we want? Envision variations in dose in terms of the individual
values of E/m for small m; these may differ from the bulk dose by many orders of magnitude
Rossi defines E/m for these small masses as the local energy density, Z
Remember that LET is dEL/dl, where l is the length along the track of the ionization source.
This might give us a handle on the effectiveness of a given bulk dose in causing damage, or it might not.
Rossi uses LET in fudging his values, as we’ll now discuss.
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Rossi’s alternative
He makes some assumptions: Particles and their secondaries deposit over
spherical volumes of specific size Source and its secondaries can deposit an
energy Ey within the sphere We call each deposition an event Event size Y is defined as Ey/d, where d is the
sphere diameter The hope is that for idealized tracks, Y will be a
constant independent of d
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How this is used
Rossi fudges the real spheres by looking at experimental systems involving spherical ionization chambers containing low-pressure gases;
These become surrogates for tiny tissue-equivalent spheres
Then he plots Y as the independent axis and the energy loss D(Y*), corrected for LET distribution
See fig. 5.6: for 1.5 µm spheres the largest D(Y*) values occur around 70 keV/µm for protons
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Local energy density Tissues have densities close to 1 g cm-3 = 103 kg m-3
Alpen shows you that the amount of locally deposited energyZ ~ 30.6 d-2 J kg-1
So for high LET and small d, this can be as high as 10.9 Gy for reasonable values of Y
For high LET radiation lots of events produce Z=0 and a few give us very big values
For low LET is more boring: the distributions are Gaussian and centered on the absorbed dose
General conclusion: high-LET radiation is harder to predict results at the single-cell level
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Demonstration That Events Don’t Interact Much
Spurs are 400 nm apart
1 nm = 10-9 m
400 nm = 0.4 m
Hydrogen radical diffusion (see below):
8 10-5cm2s-1 diffusion constant for H•
Typical lifetime 10-6s
Typical diffusion distance = 180 nm
This is smaller than the distance between spurs!
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Mozumder & Magee
[1 MeV “typical” electron] Portion of energydeposited
Spurs 6 - 100 eV 65% Blobs 100 - 500 eV 15% Tracks 500 - 5000 eV 20%
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Blobs, Spurs, and Tracks:Distribution is Energy-Dependent
Mozumder & Magee: short tracks dominate at low primary electron energy; spurs more important at high energy
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Neutrons Neutrons are produced as
byproducts of various reactions and are therefore moderately significant as portions of human or environmental exposure
We can learn things from neutron studies that will help us in understanding the ways that ions and other heavy particles interact with tissue
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Neutrons: Elastic Scatter
Important up to ~14 MeV range
average over angles:
Energy imparted to nucleus:
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How to average cos2:
Addition formula for cosine:– cos(A+B) = cosAcosB - sinAsinB– For A=B=, cos(2) = cos2 - sin2– Furthermore cos2 + sin2 = 1 so– cos2 = cos2 - (1 - cos2) = 2cos2 - 1– Therefore cos2 = (1 + cos2) / 2
This gives us the tools we need to integrate cos2 over an interval.
In general <f(x)> over an interval (a,b) is
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<cos2>, continued
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Significance in Elastic Scatter
Recall we said that for any value of q, the energy transferred to the target nucleus, Et, isEt = En (4MaMn)cos2 / (Ma + Mn)2
So the average energy imparted to the target nucleus is
<Et> = {En (4MaMn) / (Ma + Mn)2} <cos2> We just spent three pages proving <cos2>=1/2 Thus <Et> = 2EnMaMn / (Ma + Mn)2
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Inelastic Scatter
Increasingly important at higher neutron energies
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Neutrons: Other Mechanisms
(III) Nonelastic (75 MeV)
12C + n 9Be + KE ~1.75 MeV
(IV) Neutron Capture14N + n 14C + p1H + n 2H + 2.2 MeV
(V) Spallation: Nucleus fragments!
Need very high-energy neutrons ( > 100 MeV)
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Free Radicals:Definitions and Illustrations
A free radical is defined as a molecular species containing an unpaired electron. It may be charged or uncharged.
Most biological free radicals, with the significant exception of superoxide (O2
- •), are uncharged.– OH- Hydroxide ion (9 protons, 10 electrons)– OH• Hydroxyl radical (9 protons, 9 electrons)
Moses Gomberg: Characterized the triphenylmethyl radical in 1900
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Reactivity of free radicals Free radicals are reactive because the unpaired electrons
tend to seek out targets, either other unpaired electrons:H• + •H H2
… or other acceptors of unpaired electrons. Reactivities vary considerably depending on presence or
absence of stabilizing influences, such as channels through which the unpaired electron can be delocalized
In the absence of those channels, free radicals tend to recombine in picoseconds
With those channels, they can last seconds or longer, even at room temperature
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Radical Stability
This has nothing to do with political psychology :-) Highly unstable free radicals tend not to stay around
long enough for ordinary spectroscopic methods to detect.
Radicals where the unpaired electron can be highly delocalized last long enough to detect.
Triphenylmethyl radical:
CH •C + H•
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Cartoons of Electron Distributions in ions, molecules, and radicals
Hydroxyl radical(8 paired e-, 1 unpaired e-, 9 p+)
Hydroxide ion(10 paired e-, 9 p+)
Molecular oxygen(16 paired e-, 16 p+)
Superoxide ionic radical(16 paired e-, 1 unpaired e-, 16 p+)
O H:
:: •
H:
::O
:
O:
: : O:
::
O:
: : O:
::
•
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10-16 - 10-12 s Scale Events and After
e-fast + H2O H2O+• + e- + e-
fast
e-fast + H2O e-
fast + H2O* H• + OH•
H+ + OH•
(<100 eV)
H2O H2O-•nH2O e-
aqSolvatedaqueoushydrated
(10-4s)
H+
AcidH• H2
~10-11s
H2OH•, OH•, e-
aq
O• O2
O2-•, H2O2
Ionization:
Activation:
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Radiation Chemistry of Water Since biological tissue is mostly water, we’re very
interested in the products produced when water absorbs ionizing radiation
The reactive species formed out of water are responsible for a large fraction of the biological activities of radiation
Ordinary ions (H+, OH-, H3O+) are among these species, as is hydrogen peroxide (H2O2);
So are free radicals: H•, OH•, O2-•, HO2•
We often discuss the “solvated electron”, eaq-.
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Fricke Dosimeter Bookkeeping tool for aqueous radical chemistry,
based on Fe2+ Fe3++ e-
ferrous ferric Sequence of reactions:
H• + O2 HO2• (i.e. H-O=O•)HO2• + Fe2+ HO2
- + Fe3+ HO2
- + H+ H2O2
OH• + Fe2+ Fe3+ + OH-
H2O2 + Fe2+ Fe3+ + OH- + OH• In absence of O2: H• + H2O OH• + H2
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Fricke Dosimeter: bookkeeping
Each hydrogen radical H• causes the oxidation of three molecules of ferrous ion
H2O2 produced by radiolysis will oxidize two ferrous ions: one directly, one indirectly.
A radiolytically-produced OH• radical gives rise to one more oxidation
Therefore at acidic pH in the presence of oxygen,G(Fe3+) = 2G(H2O2) + 3G(H•) + G(OH•)
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Definition of Yield
G = Yield Number of events produced per 100 eV energy deposition
We’re often interested in dG(E)/dE
Yield is either dimensionless or has dimensions of (energy)-1 depending on your perspective
Fricke dosimeter provides a way of measuring yield
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Fricke bookkeeping Results on p. 112 for 60Co photons:
G(H•) = 3.65G(H2O2) = 0.75G(OH•) = 3.15
We then apply formula 6.8 to determine G(Fe3+) Recall that under appropriate conditions
G(Fe3+) = 3 * G(H•) + 2 * G(H2O2) + G(OH•)= 3 * 3.65 + 2* 0.75 + 3.15 = 15.6
Under anaerobic conditions: eqn. 6.9 applies: G(Fe3+) = G(H•) + G(OH•) + 2G(H2O2) = 8.3
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Interactions of Energetic Electrons With Biological Tissue
Direct
e-fast + DNA DNAbroken+e-
fast
e-fast + Protein Proteinbroken+e-
fast
Indirect Action
H2O* + e-fast
e-fast + H2O
H2O+• + e-H2O+e-
fast
log - lineardose - response
biol response
furtherradicalchemistry
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Direct Action: the model
Direct action of radiation on a species says that a single hit of radiation onto a molecule damages it. Then if N is the number of undamaged molecules after irradiation with dose D, we expect the change in N, N, with a small increase D in dose is proportional to N and to D.
* * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * * * * * *
N0 Total moleculesN Undamaged molecules
Radiation in
6/10/14 Rad Bio: interactions with matter p. 62 of 85
Physical model and mathematics
Let N = number of undamaged molecules after irradiation with dose D. Then dN N dD.
More radiation dose implies more response More undamaged molecules implies more
damage.
A A+ + e-
or other chemistry
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Why should the damage be log-linear?
The relationship dN N dD can be rewritten dN = -kN dD, where k = inactivation constant.
Then dN / N = -kdD. Integrating both sides, ln N = -kD + C. Raising e to a power on both sides, elnN = e(-kD+ C) = e-kD * eC. Defining eC = N0,
N = N0e-kD
Thus the physical meaning (boundary condition) of N0
is that it is the number of entities present in the case where the dose is 0.
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Significance of the inactivation constant
Inactivation constant, k, is in dimensions of inverse dose (e.g. units of Gy-1) and is the reciprocal of the dose required to reduce the number of undamaged molecules down to 1/e times the original count.
N = N0e-kD; if Di = 1/k, then N(Di)= N0e-kDi = N0e-k/k = N0e-1 = N0/e We could define a half-inactivation dose D1/2, analogous to the half-life of an emitter:
For D =D1/2, N=N0/2 = N0e-kD1/2, ln1/2 = -kD1/2
Thus -ln2 = -kD1/2,so D1/2 = (ln 2)/ k = 0.693 / k
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Indirect action of radiation
Initial absorption of radiative energy gives rise to secondary chemical events
Specifically, in biological tissue R + H2O H2O* (R = radiation)
H2O* + biological macromolecules damaged biological macromolecules
The species “H2O*” may be a free radical or an ion, but it’s certainly an activated species derived from water.
Effects are usually temperature-dependent, because they depend on diffusion of the reactive species to the biological macromolecule.
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Dose-response for indirect action
Unlike the direct-action case, we can’t write down a simple mathematical model for what’s going to happen. The dose-response curve may be log-linear, but it doesn’t have to be:
ln(S
urvi
ving
Fra
ctio
n)
Dose
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Interaction of energetic electrons with biological tissue
Direct action:e-fast + DNA DNAbroken + e-fast (log-linear)e-fast + protein proteinbroken + e-fast (log-linear)dN/dD = -k*D; Nundamaged = N0e-kD
Indirect action:H2O* + e-
fast
e-fast + H2O further radical
chemistry H2O+. + e-
H2O + e-fast
(water molecules) + (biomolecules) (biomolecules)* + radical water products
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Radical Fates/Damaged Biomolecule Fates
Recombination A• + B• A - B (timescale 10-11s)
Generally A = B i.e. A• + •A A - A Restitution: Non catalyzed regeneration of non-radical
species (microsecond timescale)
A• + X A + X•
Repair: Catalyzed regeneration of undamaged species
A• + E + R Amod + E + R• where E is enzyme (ms-sec)
biolmolecule
diffuseablebiol
out
biolbiol
Fundamentals of Biology for the Radiation Biophysicist
It would be presumptuous of me to try to summarize all of biology in half of one lecture
I’ll therefore content myself with pointing out a few fundamentals that will be relevant to our studies of the interactions between ionizing radiation and biological tissue
As an endpoint, we’re primarily concerned with the effects of radiation on vertebrate, especially human, tissues; but we do need to have some feel for how radiation affects bacteria and yeast as well
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What is life?
That was the title of a series of lectures given by Erwin Schrödinger in Dublin in 1943
His focus was on articulating how quantum physics could help to explain the organizational principles found in organisms
But we can kidnap that name to focus on what we actually do want to do, which is differentiate living organisms from non-living entities
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What are living organisms?
Entities capable of:– Reproduction– Energy processing– Adaptation to changes in environment– Capable of local decreases in entropy
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Based on that definition,what is alive?
On this basis, conventional life from archaea and eubacteria up through elephants and redwood trees are living
Viruses are a borderline case; prions highly questionable
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Organisms are made up of cells
Cells are somewhat self-contained objects within which chemical reactions and reproduction can occur
Every cell interacts with its environment Cells are surrounded by a differentially
permeable boundary called a cell membrane Sizes of cells vary but they’re generally between
1 and 10 micrometers on a side
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Highest-level taxonomic distinctions
Most fundamental distinction is made on the basis of whether the organism’s cells have nuclei
– Eukaryotic cells have nuclei– Prokaryotic (archaeal and eubacterial)
cells don’t Eubacteria are simple, generally
unicellular, organisms lacking nuclei Archaea are like that too, but they appear
to derive from a separate evolutionary history; many are extremophiles
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Eukaryotes
These organisms have nuclei and generally have other definable organelles as well: mitochondria, endoplasmic reticulum, Golgi apparatus, vacuoles, chloroplasts, …
Often but not always multicellular Yeast, e.g. Saccharomyces, is a
unicellular eukaryote Some organisms are complex but
unicellular
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Reproduction
We included this in our definition of life Unicellular organisms generally reproduce by fission,
but not inevitably; there are cooperative (sexual) events that occur even among bacteria
Multicellular organisms undergo mitosis at the cellular level but they also have a level of organization wherein an entire organism can be engendered via combinations of meiosis, mitosis, and growth
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Eukaryotic organelles
Nucleus: site of replication and transcriptioncontains DNA in various levels of organization
Mitochondrion: site of most catabolic (energy-producing) reactions, which typically yield ATP
Endoplasmic reticulum: vehicle for lipid synthesis and protein processing
Golgi apparatus: vehicle for trafficking Cytoskeleton: stiff proteinaceous organizers Vacuoles: sacs containing fluids Chloroplasts: sites of photosynthesis
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How do we study biological systems?
Observations of ecosystems Direct observations of whole organisms Recognition of tissue-tissue interactions Delineation of tissue types Recognition of cell-cell interactions Delineation of cell types Characterization of molecular events in a cell
and in the extracellular matrix Understanding of the underlying physics that
enables those molecular events to occur
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Biological activity depends on chemistry
That’s a commonplace now, but it wasn’t fully recognized until sometime in the nineteenth century
It applies to chemical transformations within cells, but it also applies to extracellular systems and macroscopic movements, such as muscle contraction
Understanding the energetics (does the activity require or release energy) and the kinetics (how does one overcome an activation barrier) is critical to understanding biochemical processes
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Biological reactions are catalyzed
A catalyst is an entity that participates in a reaction but is ultimately returned to its original state after the reaction completes
Therefore a catalyst influences kinetics but not equilibrium
Biological catalysts are called enzymes Enzymes have three fundamental properties:
– They are catalytic– They are specific– They can be regulated
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Most, but not all, enzymes are proteins
Note that many proteins aren’t enzymes The recognition that enzymes are proteins arose in
the 1920’s and 1930’s By the 1970’s it became clear that certain RNA
molecules are catalytic Some RNA-catalyzed reactions, notably the creation
of new protein molecules, are central to biological function
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DNA is the vehicle for heritance
Deoxyribonucleic acid is a polymer found in all organisms and many viruses
Building blocks: phosphodeoxyribose backbone,N-containing side-groups called nucleic acid bases
DNA contains information enabling parent cell or organism to produce nearly-identical offspring
Differences arise from:– Mutations– Recombination– Sexual segregation of chromosomes– Epigenetic effects
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Central dogma, modern form
DNA becomes replicated prior to each cell division– Double-stranded DNA uncoils– Fresh copy of each strand created and coiled up
DNA is transcribed into various forms of RNA– Gene transcribed when RNA is called for– One strand of DNA provides template
Messenger RNA is translated at ribosome:– mRNA sequence defines amino acid sequence of
resulting protein– Protein then folds, either spontaneously or not
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DNA replication is protected against error
Inherent error rate might be one base substitution in 104 or 105 replicated bases
Error correction within DNA polymerase drops that to about 1 in 107
Further error correction (“repair”) by external enzymes drops it to about 1 in 109
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Why is that relevant?
In the human genome, 1 in 109 is still several surviving base substitutions in each replication!
Most substitutions are harmful; most aren’t fatal Exposure to ionizing radiation and certain
chemical mutagens, particularly at certain stages in the cell cycle, can significantly increase the error rate
Human genetic conditions that hinder DNA repair substantially increase radiation sensitivity
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