IONIZATION AND FRAGMENTATION OF DNA, RNA COMPONENS INDUCED BY PROTON IMPACT

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IONIZATION AND FRAGMENTATION OF IONIZATION AND FRAGMENTATION OF DNA, RNA COMPONENS INDUCED BY PROTON IMPACT DNA, RNA COMPONENS INDUCED BY PROTON IMPACT P.Moretto-Capelle, A.Le Padellec, M.Richard-Viard, J.P.Champeaux and P.Cafarelli Laboratoire Collisions, Agregats, Reactivité (UMR5589 CNRS-Univ.Paul Sabatier Toulouse 3) IRSAMC 31062 Toulouse cedex 9, France Damages induced by ionizing radiation can directly be linked to alteration of the DNA molecule. In this work, we investigate interactions between protons and phase gas DNA/RNA bases and nucleoside Energy loss by a proton in matter? Example of transport of 100 MeV proton in liquid water Important dose deposition in a well defined spatial zone Bragg Peack (BP): PROTONTHERAPY Maximum dose: proton decellerated around 100keV: maximum LET Corresponding DNA damages: evoluated Monte-Carlo codes (Nikjoo,O’Neill, Terrisol, Goodheart Rad.Env.Biophys (1999)38), we used more simpler MCDS program whose coefficients are fitted on MC codes. (Semennenko, Steward Rad.Res. (2004) 161) 10 100 10 -21 10 -20 10 -19 10 -18 D D C S (c m 2 eV -1 sr -1 ) E lectronic energy (eV ) 100 keV 50 keV 25 keV Thy FROM BASES DAMAGES EMISSION OF SECONDARY ELECTRONS Damages induced by secondary electron depend on kinetic energy: Need to know energy spectrum of the emitted electrons BUT also the absolute yield (cross section) Low energy (<20eV): dissociative attachment High energy(>20eV): ionization,fragme ntation -40 -30 -20 -10 0 10 20 30 40 0 10 20 30 40 50 60 70 80 X mm D e p th (m m) 1 10 100 1000 10000 100000 0 10 20 30 40 50 60 70 80 D epth (m m) P ro to n E n erg y (keV ) 1 10 100 1000 10000 100000 0 20 40 60 80 P ro to n E n erg y (keV ) LET (keV/ m) O u r accelerato r en erg y ran g e 100 1000 10000 100000 0.1 1 10 100 % DNA dam ages P ro to n E n erg y (keV ) BD SSB SSBp 2SSD DSB DSBp DSBpp Range around 100keV is interesting=> ultra thin target=> biomolecule in gaz phase 120 130 140 150 160 170 180 190 200 210 220 230 240 250 0 100 200 300 400 500 600 700 800 900 1000 TOWARDS ELEMENTARY STRAND BREAK: Irradiation of URIDINE 0 10 20 30 40 50 60 70 80 90 100 110 120 0 10000 20000 30000 40000 C ounts Additi vi ty? Destruction of the sugar=> Strand Break RADIOSENSITIZER? PHYSICAL MECHANISMS? 1-PHYSICAL Studies at molecular scale (… gaz phase) fragmentation patterns, electronic emission, corresponding cross sections Difference with ‘standart’ molecules? 2-IRRADIATION of DNA (plasmid) deposited SURFACE without and with molecule Carboplat ine Cisplatine Halo-Uracil (F,Br,I) ANALYSIS OF STRAND BREAKS: LINKS? Measurment of electron spectra: majority of low energy electrons Caracterization by CTMC modeling: -Total cross sections -Yield in angle and energy 10 100 0 2 4 6 8 S15 S35 S55 S75 S 95 S 135 S 155 S 175 D D C S (arb.u nit) E C C peack Many small molecules are formed PHYSICAL STAGE OF THE INTERACTION (fs): PRODUCTION OF DATA Formation of numerous small fragments: - Identification and branching ratio Can interact with neighbouring structures Number of molecule / base pair ? SRIM 2006 Moretto-Capelle, Le Padellec, Phys.Rev.A (2006)

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IONIZATION AND FRAGMENTATION OF DNA, RNA COMPONENS INDUCED BY PROTON IMPACT. P .Moretto-Capelle, A.Le Padellec, M.Richard-Viard, J.P.Champeaux and P.Cafarelli Laboratoire Collisions, Agregats, Reactivité (UMR5589 CNRS-Univ.Paul Sabatier Toulouse 3) IRSAMC 31062 Toulouse cedex 9, France. - PowerPoint PPT Presentation

Transcript of IONIZATION AND FRAGMENTATION OF DNA, RNA COMPONENS INDUCED BY PROTON IMPACT

Page 1: IONIZATION AND FRAGMENTATION OF  DNA, RNA COMPONENS  INDUCED BY PROTON IMPACT

IONIZATION AND FRAGMENTATION OFIONIZATION AND FRAGMENTATION OF DNA, RNA COMPONENS INDUCED BY PROTON IMPACTDNA, RNA COMPONENS INDUCED BY PROTON IMPACT

P.Moretto-Capelle, A.Le Padellec, M.Richard-Viard, J.P.Champeaux and P.Cafarelli

Laboratoire Collisions, Agregats, Reactivité (UMR5589 CNRS-Univ.Paul Sabatier Toulouse 3) IRSAMC 31062 Toulouse cedex 9, France

Damages induced by ionizing radiation can directly be linked to alteration of the DNA molecule. In this work, we investigate interactions between protons and phase gas DNA/RNA bases and nucleoside

Energy loss by a proton in matter? Example of transport of 100 MeV proton in liquid water

Important dose deposition in a well defined spatial zone Bragg Peack (BP):

PROTONTHERAPY

Maximum dose: proton decellerated around 100keV: maximum LET

Corresponding DNA damages: evoluated Monte-Carlo codes (Nikjoo,O’Neill, Terrisol, Goodheart

Rad.Env.Biophys (1999)38), we used more simpler MCDS program whose coefficients are fitted on MC codes. (Semennenko, Steward Rad.Res. (2004) 161)

10 10010-21

10-20

10-19

10-18

DD

CS

(cm

2 eV-1

sr-1

)

Electronic energy (eV)

100 keV 50 keV 25 keV

Thy

FROM BASES DAMAGES

EMISSION OF SECONDARY ELECTRONS

Damages induced by secondary electron depend on kinetic

energy:

Need to know energy spectrum of the emitted electrons

BUT also the absolute yield (cross section)

Low energy (<20eV): dissociative attachment

High energy(>20eV): ionization,fragmentation

-40 -30 -20 -10 0 10 20 30 400

10

20

30

40

50

60

70

80

X mm

Dep

th (

mm

)

1 10 100 1000 10000 1000000

10

20

30

40

50

60

70

80

Dep

th (m

m)

Proton Energy (keV)

1 10 100 1000 10000 1000000

20

40

60

80

Proton Energy (keV)

LET

(keV

/m

)

Our accelerator energy range

100 1000 10000 100000

0.1

1

10

100

% D

NA

dam

ages

Proton Energy (keV)

BD SSB SSBp 2SSD DSB DSBp DSBpp

Range around 100keV is interesting=> ultra thin target=> biomolecule in gaz phase

120 130 140 150 160 170 180 190 200 210 220 230 240 2500

100

200

300

400

500

600

700

800

900

1000

TOWARDS ELEMENTARY STRAND BREAK: Irradiation of URIDINE

0 10 20 30 40 50 60 70 80 90 100 110 1200

10000

20000

30000

40000

Counts

Additivity?

Destruction of the sugar=> Strand Break

RADIOSENSITIZER? PHYSICAL MECHANISMS?

1-PHYSICAL Studies at molecular scale (… gaz phase)

fragmentation patterns, electronic emission, corresponding cross sections

Difference with ‘standart’ molecules?

2-IRRADIATION of DNA (plasmid) deposited SURFACE

without and with molecule

Carboplatine Cisplatine Halo-Uracil (F,Br,I)ANALYSIS OF STRAND BREAKS:LINKS?

Measurment of electron spectra: majority of low energy electrons

Caracterization by CTMC modeling:-Total cross sections-Yield in angle and energy

10

100

0

2

4

6

8

S15S35

S55S75

S95S135

S155S175

DDCS (arb.unit)

ECC peack

Many small molecules are formed

PHYSICAL STAGE OF THE INTERACTION (fs): PRODUCTION OF DATA

Formation of numerous small fragments:- Identification and branching ratioCan interact with neighbouring structures

Number of molecule / base pair ?

SRIM 2006

Moretto-Capelle, Le Padellec, Phys.Rev.A (2006)