Nigel MasonNigel Mason

The Open UniversityThe Open University

The Atomic and Molecular Database for Radiation Damage –

How COST Nano - IBCT can help

What is the current status of What is the current status of

the field of radiation damge ?the field of radiation damge ? Our studies in Our studies in the mechanismsthe mechanisms of of

radiation damage has developed radiation damage has developed rapidly in the last decade.rapidly in the last decade.

For example role of DEA in DNA For example role of DEA in DNA damage damage

What is the current status of What is the current status of

the field of radiation damge ?the field of radiation damge ? Development of new cancer therapies Development of new cancer therapies

eg carbon ions.eg carbon ions.

HENCEHENCE

Recent research has stressed the Recent research has stressed the need to understand radiation need to understand radiation damage at damage at the molecular level the molecular level This This was aim of RADAM action 2003-was aim of RADAM action 2003-20082008

This has been coupled with the This has been coupled with the

need to understand effects of low need to understand effects of low dose long term exposure (EU dose long term exposure (EU RISCRAD programme)RISCRAD programme)

Three Grand ChallengesThree Grand Challenges

1.1. Understanding fundamental Understanding fundamental interactions between different interactions between different types of radiation and biomoleculetypes of radiation and biomolecule

2.2. Study of damage to DNA and other Study of damage to DNA and other macromolecules in the cellmacromolecules in the cell

3.3. Developing models of such damage Developing models of such damage for use in therapy etc. for use in therapy etc.

Radiation Damage – the Radiation Damage – the mechanismmechanism

What we need to understand is the What we need to understand is the mechanisms by which strand breaks mechanisms by which strand breaks in DNA occur.in DNA occur.

Can this be understood by single Can this be understood by single collisions ?collisions ?

Is the damage located at specific sites Is the damage located at specific sites in the DNA chain ?in the DNA chain ?

Can we ‘control’ the site & amount of Can we ‘control’ the site & amount of damage ? damage ?

or X e-

<20 eV

Single and double strand breaks may be induced by secondary

species: a large number of secondary electron with kinetic energies

below about 20 eV, are produced along the radiation track

Damage of the genome in living cell by ionising radiation is about 1/3 a

direct and 2/3 an indirect processes.

Radiation damage to DNA

Electron induced damage of DNAElectron induced damage of DNA

V(R)

0

A + B + e-

A- + B

R

D(A-B)

EA(A)

e- + AB → (AB)-*

Transit negative ion (TNI)

→ AB-

→ AB + e-

→ A- + B

autodetachment

molecular anion

dissociative electron attachment

Dissociative Electron Attachment

Thymine + e- → TNI-* →electron attachment

C5H6N2O2-

e-dissociative electron attachment

(T-H)- + H(T-2H)- + neutral(s)

C4H5N2O- + neutral(s)

C2H3N2O- + neutral(s)

C3H2NO- + neutral(s)

CN- + neutral(s)

O- + neutral(s)H- + neutral(s)

OCN- + neutral(s)

→→→

→→

→C3H4N- + neutral(s)

→

→

→

→

DEA to biomolecules

126 amu

125 amu

124 amu

1 amu

16 amu

26 amu

42 amu

54 amu

68 amu

99 amu

73 amu

0 1 2 3 40

2

4

6

8

10

12

Cro

ss s

ectio

n (1

0-20 m

2)

Electron energy (eV)

H loss

e-

DEA in Thymine

(M-H)-

125 amu

Site selectivity and Chemical control

• Such site selectivity appears to be maintained in larger biomolecules

• Eg if add sugar to base (thymidine) can still target thymine site

• So DEA indicates radiation damage can be explained at a molecular level

DEA and radiosensitizers

• Can we exploit such site specific damage ?

• Eg in developing new cancer therapies ?

• Consider radiosensitizers

• Au nanoparticles

E.g exploit enhanced DEA to develop new radiosensitizers

5-nitrouracil

So exploit enhanced DEA to develop new radiosensitizers 5-nitrouracil

0 1 2 30

5000

10000

0 5 100

3

6

0 5 100

30

60

0 5 100

100

200

0 1 2 30

30000

60000

0 1 2 3 40

5000

10000

0 2 4 6 80

25

50

0 2 4 6 8 100

500

1000

(5NU-H)-

156 Da

a b (5NU-2H)-

155 Da

c(5NU-O)-

141 Da

d (5NU-OH)-

140 Da

e f (5NU-NO2-H)-

110 Da

0 5 10 15 20

gC

3N

2OH-

82 DaC

3N

2O

2

-

96 Da

h

(5NU-NO2)-

111 Da

Ion

yie

ld (

cp

s)

Electron energy (eV)

0 5 10 15 20

SO !!!

• We are now developing a picture of radiation damage that is based on fundamental collision physics

• Such an understanding may/is leading to opportunity for controlling damage pathways

• Exploitation for new radiotherapy techniques ?

But are we asking the right questions ?

We need to provide data that is useful in setting clinical protocols

• Medical applications require accurate dose evaluation performed using models

• Available simulation codes (MCNPX, PARTRAC, PENELOPE, GEANT-4): Based on high-energy particle approximations, few molecular details are included

Energy degradation of electrons in H2O

Energy scale (eV)

H2O , 200 Torr

5 mm

2 keV incident energy

(5 single tracks)

Different types of interactions

2 keV electrons in H2O Pressure: 200 Torr

5 single tracks

Ionisation

Neutral dissociation

Excitation

Auger

Such models need

• Cross sections !!!!

• Real numbers not just phenomenology !

Database assessment --What data is needed ?

Electron impact processes• Energy resolved cross sections• Dissociation/ionisation processesIon molecule interactions • Charge state • Energy dependence• Fragmentation – branching ratiosPhoton interactions X-ray to UVSpectroscopy – photostability

Data providers * theory * experiment

Data users in variousapplication fields * fusion science * astrophysics * industrial plasmas * environmental physics * medical (radiotherapy) etc.

Data centers data compilation data evaluation (important but not easy) dissemination and updating of database retrievable online database = easy to access, use, find data

Data

requests

Dat

a ne

eds

Data

pro

vid

e

Dat

a pr

ovid

e

Dat

a se

arch

Data requestedD

ata

search

for

check

International A&M data center network IAEA, NIFS, A-PAN, KAERI, NIST, ORNL, GAPHIOR, VAMDC,

Data provided

feed

back

Views from Database assessed data on cross sections

Electron interactions data in H2O

Summary of the Recommended data on the electron collision cross section for H2O

Y. Itikawa and N.J.Mason, J. Phys. Chem. Ref. Data 34 (2005)1

Total electron scattering and ionisation cross sections in H2O

Total

Ionisation

100%Discrepancy below 5eV

*Muñoz et al., Phys. Rev. A

(2007)

e-H2O integral cross section data (Courtesy of G Garcia)

1 10 100 1000 10000Electron energy (eV)

0.01

0.1

1

10

100

1000C

ross

sec

tion

(a02

)Total scattering

(5%)

Integral elastic and inelastic

(10%)

Ionisation (7%)

Excitation (15%)

Neutral dissociation

(15%)

Elastic scattering - H2O

1

10

0 30 60 90 120 150 180

Present

Rescigno & Lengsfield (1992)

Okamoto et al (1993)

Gianturco et al (1998)

Varella et al (1999)

DC

S (

10-1

6 cm

2 sr-1

)

Scattering Angle (degrees)

10 eVElastic

0.1

1

10

0 30 60 90 120 150 180

Present (CNU)Johnstone & NewellRescigno & LengsfieldOkamoto et alGianturco et alVarella et al

DC

S (

10-1

6 cm

2 sr-1

)

Scattering Angle (degrees)

6 eVElastic

0.1

1

10

0 30 60 90 120 150 180

Present

Shyn & Cho

Varella et al.

Dif

fere

nti

al C

ross

Sec

tion

(10

-16 c

m2 s

r-1)

Scattering Angle (degrees)

4 eVElastic

Cho, Park, Tanaka, BuckmanJPB 37 625 (2004)

But what is the measurable in clinic ?

The stopping power: (-dE/dx)

Mass stopping power of electrons in water: -dE/ dx (Munoz et al)

But such complete data sets are rare

For most biomoleules MOST cross sections are missing

Some may be calculated – eg ionisation (Theory – Kim (BE) and Deutsch Maerk )And compare well with experiments(But note kinetic effects in products)

Or for total, elastic, some excitationsQuantemol package (J Tennyson)

But….

• To date most of the ideas are based on knowledge in gas phase

• The cell is not a gas !! For example electronic states are shifted !

• So are gas phase cross sections relevant in modelling radiation damage in a cell ?

Water ice Note : Blue shift in the solid phase

0.0E+00

2.0E-18

4.0E-18

6.0E-18

8.0E-18

1.0E-17

1.2E-17

1.4E-17

1.6E-17

1.8E-17

2.0E-17

6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5

Photon Energy / eV

Cro

ss S

ectio

n

/ cm2

Carbon dioxide Note : Blue shift in the solid phase

0.0E+00

2.0E-19

4.0E-19

6.0E-19

8.0E-19

1.0E-18

1.2E-18

1.4E-18

6.5 7 7.5 8 8.5 9 9.5 10 10.5

Photon Energy / eV

Cro

ss S

ectio

n / c

m2

Comparison of gas and solid phase Methylamine

Note absence of low lying bands in solid phase

Energy (eV)

5 6 7 8 9 10 11

Cro

ss S

ectio

n (

cm

2 )

0

1e-18

2e-18

3e-18

4e-18

5e-18

6e-18

7e-18

Gas PhaseSolid Phase

Cross sections in condensed phase

• TRK sum rule still holds !!

• So where does ’lost flux’ go ?

• How to measure cross sections in condensed phase ?

Studies in condensed phase

• Evidence is that same site selectivity etc holds in condensed films

GCAT

GCAT

G+C+A+TG+C+A+T

EA - electron affinityEA(CN)= 3.82 eVEA(CNO)= 3.61 eV

DEA to oligomers

O

PO-

NH2

N N

NNHO O

O

O

NH2

O

N

N

P

OO OO-

O

O NH2

N

N

N

N

NN

O

O

O

OO

O

O-

O

OH

G

C

A

Toligomertetramer

(1172 amu)

P

CN- CNO-Gas phase

Condensed phase

Studies in condensed phase

• Evidence is that same site selectivity etc holds in condensed films

• Cross sections in ice have been defined (Sanche)

But a cell is not a solid either !

• So what is the best mimic of the environment of biomolecules in a cell ?

• What can be explored in the Lab ?

Experiments with clusters • Groningen University

T Schladtholter et al)

• Ion irradiation of biomolecular clusters

• Eg C+ on nucleobasesDeoxyribose and amino acids

Uracil and Thymine Different fragmentation

patterns

Experiments with clusters

• Experiments in He droplets (Innsbruck)

• But is this a mimic of ‘real conditions’ ?

But what about other biomolecules ?

• DNA is not the only target in the cell !!!

• What about other molecules ?

What is the role of water and proteins in electron induced damage of DNA?

DNA

Proteins (amino acids)

M. Begusova et al., Int. J.Radiat.Biol. (2003)

bases

sugar

undamage atoms

proteins

undamage atoms

DNA

proteins

• Free electron attachment to amino- acids/nucleobases complexes

• radiation damage of proteins

radiation

What is the effect of damage to the cell membrane ?

• radiation damage of proteins

But what about other biomolecules ?

How do we study Lipids and proteins ?

In gas phase or on surfaces ?

Damage may change ion transport through cell membrane !

Direct damage vs Indirect

• All of the discussion so far is based on direct damage but this is only 1/3 of the damage !

• What about mechanisms of indirect damage ?

And no description can ignore repair

• So in reality we are only exploring one part (important though it is) of the radiation damage process

And we have more to explore with new projectiles

• What about damage induced by positrons ??

• How do positrons damage DNA ?

• Role of annihilation and gamma rays ?

So lots of data needed !

• How do we co-ordinate data collection ?

• Where does the user find it ?

• When collected how/where is it stored and ‘ratified’ ?

VAMDC is funded under the “Combination of Collaborative

Projects and Coordination and Support Actions” Funding

Scheme of The Seventh Framework Program.

Call topic: INFRA-2008-1.2.2 Scientific Data Infrastructure.

Grant Agreement number: 239108.

• VAMDC will provide a scientific data

e-infrastructure enabling easy access to A+M

resources

• Http://www.vamdc.org/

Atomic & Molecular data underpins a wide range of basic and applied research and industrial development

•Thus there is a need to collect, assess and allow access to a wide range of A&M data

•Hence there many A&M related DATABASES have been developed but such databases are….

•Often in different formats •Access maybe restricted or ‘regional’•Often fragmentary providing ‘partial resource’

So need a common portal ‘single point entry’ to access multiple databases for comprehensive data mining.

KEY VAMDC OUTCOMES Develop or/and extend standards for

interoperability of AM resources Implementation of selected databases /

Compatibility with existing extraction tools

Find resources easily Registries at a fine granularity

Query those resources Query protocols or/and languages

Transfer large quantities of data, Asynchronous Queries

Create a safe environment where latest AM data can be easily published (even small sets)

Linking producers and users

KEY BENEFITS to usingVAMDC

Find any type of A&M data with a “click”

Uniform access, i.e. saving time with format of data, tools development

Allows cross-matching of different sets of A & M data

Allows wide access to the latest published AM data

This then allows

Increased level of scientific analysis

VAMDC must meet the users requirements but also the producers requirements

VAMDC must be built in collaboration with many A&M specialists

A&M users (and data providers)

VAMDC has, in its first year, sought to engagewith its ultimate user base through meetings andworkshops and this session reviews some of thoselinks

A & M Users – VAMDC clientele

– Astrophysics/Astronomy/Planetary Science– Atmospheric Science– Fusion– Plasma Science– Radiation science

Astronomy/ Planetary Science

Main providers of VAMDC project

Data to interpret observations

and develop models

Many databases exist and are in VAMDC

Astronomy/ Planetary Science

A&M Data needs increase with:

• New projects e.g. ALMA

• Developing science (e.g. exoplanet atmospheres)

Planetary Science

Recent examples of A&M data

• Titan atmosphere• Surfaces of Saturnian moons

• Physical and Chemistry of KBOs

Need ice spectra - Ghosst

Linking to other EU projects

Europlanet/ IDIS project

Lassie (Training Network)

COST Chemical Cosmos

Helio

Great (Training Network)

Atmospheric Science

One of worlds largest and

most controversial fields of science

Global Warming – Climate Change

Pollution and health – legislation

Major observational programme –

Remote sensing

Atmospheric Science

Global Warming – Molecular spectra

Photoabsorption cross sections

Pollution/ aerosols – Chemical reactions

Remote sensing - IR and UV spectra

Instrumentation – Analytical tools for legislation 4 5 6 7 8 9 10 11

Energy [eV]

Cro

ss s

ectio

n [M

b]

Atmospheric Science

Well provide with databases

HITRAN

Integrate VAMDC & Hitran

UV/Vis+ Spectra Data Base

Fusion Science

ITER one of the worlds largest science projects

A&M central to its engineering

IAEA have supported A&M databases for decades

Fusion Science

IAEA AMDIS ALADDDIN database

A&M data and particle surface interactions

E.g. To design negative ion sources

Plasma Science

Industrial development

Device fabrication, pollution control, lighting, medicine

A&M data need in plasma

simulations

Plasimo and Quantemol-D

The ideal of a virtual factory

Plasma science

• A&M data needed for modelling• New feed gases for ‘greener’ world• Nanotechnology =

atomic/molecular scale• Cross sections/rate constants needed

VAMDC support for Workshops on plasma processing and lighting ESCAMPIG July 2010

Radiation damage

Development of next generation

therapy and understanding risk

(e.g. effect of low dose but long term exposures – topical with Japan!)

Radiation damage

Uses simulation codes (MCNPX, PARTRAC, PENELOPE, GEANT-4)

Requires A & M data input

(G Garcia presentation)

Radiation damage

• A&M data needed for track modelling• Biological material is represented by gases

(Tissue equivalent material)• Setting protocols so need approved datasets• Solid state/liquid cross sections needed

VAMDC support for Workshop June 30-July 3, 2010 led to;

• Special volume being published• New Cost Action will include working

group data assembly and• Recommendations – link to

fusion/Euratom programme

VAMDC therefore has to

Engage with users and providers Disseminate its product Sustain itself

Then….

VAMDC has the potential to be the tool of primary choice for users of A&M data worldwide

To be the ‘google’ for A&M