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Biological radiation effects

Gerda HorneckDLR, Institute of Aerospace Medicine (retired)

PPOSS Biological Contamination Prevention Workshop, DLR, Köln, 23-25 January 2017

PPOSS – Biological radiation effects

Ionizing radiation-matter interaction


Ionizing radiation consists of X-rays, gamma rays or particles with sufficient energyto cause ionization in the medium through which it passes

Energy spectrum of electromagnetic radiation Particle energy (MeV)

10-1100101102103104105106107108

Particle fl

ux (particl

e / cm2 s st

er)

10-8

10-7

10-6

10-5

10-4

10-3

10-2

10-1

100

101

102

103

104

105

106

107

electrons (radiation belt)

solar particle events

protons

(radiation belts)

galactic

cosmic

radiation

Energy spectrum of cosmic particle radiationin Low Earth Orbit

solar maximum

solar minimum


Modes of energy transfer in matter by ionizing radiation:

Photo-absorption: Photon transfers its energy to an electron which leaves the atomCompton-effect: Photon collides with a target, which releases loosely bound electrons from the outer shell of the atom (scattered electron and photon).Pair production: Photon induces pair electrons of opposite charge; electron and positronNuclear process: Photon leads to disintegration of the nucleus by release of neutrons and protons

Photo- Compton- Pair- Nucleareffect effect production process

Increasing energy

Fritz-Niggli, Strahlengefährdung/Strahlenschutz, 1988


Radiation measurements and units:

1. Physical dose: (Gray) absorbed dose per mass unit1 Gray = net absorption of 1 Joule in 1 kg of water

2. Quality factor: The quality factor considers the relative biological effectiveness of radiation (RBE), which is dependent on the linear energy transfer (LET) of the radiation

3. Biologically effective dose: (Sievert) dose equivalentThe dose equivalent is calculated as the product of absorbed dose in tissue multiplied by a quality factor and then sometimes multiplied by other necessary modifying factors at the location of interest.


Biological responses to ionizing radiation


Radiobiological chain of events within a biological cell with two alternative pathways of radiation damage, resulting in either direct or indirect radiation effects


Dose-effect curve (Survival curve): N/N0= e-kD

1. D37 value: radiation dose of X-rays required to reduce survival to 1/e, i.e. 37%.

2. D10 value: radiation dose (kGy) required to reduce the survival rate by 10-fold (one log cycle) (from the exponential part of the curve only)

3. Dq value: (Quasi-threshold dose) Dose, determined by extrapolation of the exponential part of the curve to 100 % survival (for shoulder curves only)

D10 value 0.1 kGy 1.4 kGy 2.8 kGy

Horneck et al. 2006, Radiation Biology, in: Fundamentals of Space Biology, Clément and Slenzka (eds.) Microcosm Press and Springer. pp- 291-336

Dq value

PPOSS – Biological radiation effectsD10 values for microbial systems (bacteria and viruses) after irradiation (low LET radiation)

to be discussed later


Finding I:

Biological responses to radiation:

• DNA is the most sensitive target of ionizing radiation

• Radiation damage to DNA may lead to inactivation, mutation etc.

• The biological effectiveness of ionizing radiation depends on the capacity of the biological system to cope with the primary radiation damage (repair capacity)

• The D10 value describes the radiation sensitivity of the organism under consideration


Role of the quality of ionizing radiation


Biological weighting of ionizing radiation: The biological radiation effect depends on the density of ionizations, the Linear Energy Transfer (LET), which is the energy actually deposited per unit distance along the track (i.e., -dE/dx).

Energy distribution of radiation of different LET

but of the same dose hitting a biological cell

Relative biological effectiveness RBE:

• RBE describes the dependence of the

biological effectiveness on LET.

• RBE is the ratio of the physical doses of

the test radiation (Dt) and e.g. X-rays

(Dx), leading to the same biological

effect:

RBE= Dx/Dt


Fe

Ar

He

RBE for different accelerated heavy ions (He, Ar, Fe) irradiating spores of Bacillus subtilis

wild type

repair deficient

Moeller, R. et al. (2008). J. Bacteriol. 190: 1134-1140

repair deficientRBE


Biological weighting of ionizing radiation: • The quality factor is a generalized approximation of RBE based on LET.


Finding II:

• The biological effectiveness of ionizing radiation depends on its quality, i.e. the density of ionizations, the Linear Energy Transfer (LET)

• RBE describes the dependence of the biological effectiveness on LET of a radiation relative to a standard radiation, e.g. X-rays

• The quality factor is a generalized approximation of RBE based on LET


Radiation measurements and units (to keep in mind):

1. Physical dose: (Gray) absorbed dose per mass unit1 Gray = net absorption of 1 Joule in 1 kg of water

2. Quality factor: The quality factor considers the relative biological effectiveness of radiation (RBE), which is dependent on the linear energy transfer (LET) of the radiation

3. Biologically effective dose: (Sievert) dose equivalentThe dose equivalent is calculated as the product of absorbed dose in tissue multiplied by a quality factor and then sometimes multiplied by other necessary modifying factors at the location of interest.


Biological effects of galactic cosmic radiation


Galactic cosmic radiation (GCR): Percent contribution from individual GCR elements in solar minimum to particle flux (●) radiation dose (Δ) weighted by the square

of the charge Z of the particle

dose equivalent (■), i.e. absorbed dose multiplied by a quality factor

Cucinotta (2003) Gravitational and Space Biology Bulletin, 16(2)

HZE particles have high biological effectivenessIron ions have the highest biological effectiveness

HZE particles


• ~2x103 protons per 100 µm2 per year • ~ 0.6 Fe-ions per 100 µm2 per year

(at energies of 200-700 MeV/u)

However ! Low chance to be hit by an HZE particle of GCR:

Mammalian cell

Cross section of cell nucleus :about 100 µm2

Bacterial cellCross section about 1 µm2

• ~ 20 protons per year • ~ 0.006 Fe-ions per year(at energies of 200-700 MeV/u)


Flown on Apollo 16, 17, ASTP, EURECA, LDEF, Spacelab 1

Biostack experiments: To study biological effects of single HZE particles of GCR


Spores of Bacillus subtilis Integral net fraction of inactivated spores as function of the impact parameter, i.e. the radial distance from the HZE particle trajectory (left scale) (results from ASTP mission, Apollo-Soyuz Test Project)

Biostack experiments: To study biological effects of single HZE particles of GCR

Long ranging effectLong ranging effect

Facius et al. 1994, Adv. Space Res. 14, 1027

Size of spore


STARLIFE – an international campaign to study the role of galactic cosmic radiation in astrobiological model systemsTypes of radiation: • Heavy ions (He up to 1kGy, Si up to 1kGy, Ar up to 1 kGy, Fe up to 2 kGy), • X-rays up to 2 kGy• -radiation up to 117 kGy

Test systems:• Radiation resistant bacteria: Deinococcus spp.• Halophilic archaea: Halobacterium salinarum ,

Halococcus hamelinensis, Halococcus morrhuae• Cyanobacteria: Chroococcidiopsis spp,

Synechocystis spp.

• Fungi: Cryomyces antarcticus• Lichens: Xanthoria elegans, Circinaria gyrosa• Tardigrades: Richtersius coronifer• Rotifers: Mniobia russeola

Moeller et al. 2017, Astrobiology, special issue, in press

Experiments at heavy ion accelerators, simulating HZE particles of GCR (as resort)


Finding III: • GCR consist of 85 % protons, 14 % alpha particles (helium

nuclei), 1 % HZE particles (particles of High charge Z and high Energy)

• HZE particles of galactic cosmic radiation have the highest biological effectiveness

• The Biostack experiments allow to determine the biological effectiveness of single HZE particles of GCR

• Experiments at heavy ion accelerators, e.g. STARLIFE, provide information on the effectiveness of cosmic HZE particles, although applied at much higher fluxes


Role of the environment during irradiation


Radiobiological chain of events: Role of the environment during irradiation

, water activity, gravity


Impact of low temperature on radiation responses ( rays)

• Increased radiation resistance at low temperatures

• There is no difference in radiation responses at temperatures < 120 K

• Radiation sensitivity was further increased if the cells were exposed to O2 after irradiation (O2 effect)

Spores in H2O, irradiation in

N2, then in O2

Spores in D2O,

irradiation in N2,

then in O2

Spores in H2O, irradiation in

N2, then in H2S

Spores in D2O, irradiation

in N2, then in H2S

Powers, Tallentire, 1968, The roles of water in the cellular effects of ionizing radiations, in: Action Chimiques et Biologiques des Radiations, M. Haissinsk ed., Masson Paris, Vol. 12, pp. 3-67.

Bacillus megaterium spores


Impact of low temperature on radiation responses

FZ Jülich, Roessler et al.


Impact of low temperature on radiation responses17 MeV Protons

Escherichia coli

20 MeV Helium

Salmonella typhimurium

• Increased radiation resistance at low temperatures

• Reduced mutagenic efficiency at low temperatures

• Possible mechanisms: OH-radicals are

immobilized at <100 K H-radicals remain mobile

at >14 K and re-unite with the immobilized radicals

Modified radiation products (?)

D10=3.6 kGy

D10=0.3 kGy

D10=150 Gy

D10=80 Gy

Horneck, Kozubek, Roessler, (unpublished)


Impact of low water activity (desiccation) on radiation responses (simultaneous expose)

Control, wet, 760 Torr

Irradiation at 10-5 Torr(~10-3 Pa)

multilayer, naked, 10-5 Torr

monolayer, naked, 10-5 Torr

• Increased radiation sensitivity at low pressure (vacuum) of cells in monolayers without any protection

• Effect at low pressure (vacuum) was reduced if saline, NB or glucose were added before desiccation and irradiation.

• Possible mechanisms: The chemical additives

diminished the desiccation process

monolyer, saline, 10-5 Torr

monolayer, glucose, 10-5 Torr

monolayer, NB, 10-5 Torr

D10=82 Gy

D10=22 Gy

Escherichia coli B/r

Bücker and Horneck, 1969, Biophysik, 6, 69


Impact of weightlessness on radiation responses (Results from IML-2 mission)

Rejoining of DNA strand breaks in X-irradiated cells of E. coli B/rduring incubation in weightlessness

Induction of SOS response in X-irradiated cells of E. coli PQ37during incubation in weightlessness

Horneck et al. (1996) J. Biotechnol. 47, 99Long ranging effect

No impact of weightlessness on repair efficiency


Impact of exposure time on radiation responses (Results from LDEF mission after 6 years in space

Spores of B. subtilis Radiation dose: 4.8 Gy


Impact of exposure time on radiation responses of B. subtilis spores(Results from space missions)

Mission Duration of vacuum exposure

Survival fraction at end of exposure in thin layers

(%)

Survival fraction at end of exposure in thick layers and

presence of protective sugars

(%)

References

in space ground control

in space ground control

SL 1 10 d 69.3 15.8 85.3 2.6 n.d. n.d. Horneck 1993

EURECA 327 d 32.1 16.3 32.7 5.6 45.5 0.01 62.7 8.2 Horneck 1995

LDEF 2 107 d 1.4 0.8 5.4 2.9 67.2 10.2 77.0 6.0 Horneck et al. 1993, 1994

EXPOSE 1.5 a


Impact of exposure time on radiation responses

Example: LithopanspermiaTime calculated for D. radiodurans R1 to reach a survival rate of 10-6 based on a D10 value of 1kGy

Mileikowsky et al. 2000, Icarus, 145, 391


Finding IV: Role of environment on radiation responses

Irradiation at • low temperature increased the radiation resistance• low pressure (vacuum) decreased the radiation resistance• weightlessness did not change the radiation responses

Long-term exposure to space including GCR:• Spores of B. subtilis survived 6 years in space (GCR dose = 4.8 Gy)• Shielding of >250 g/m² (> 80 cm of rock) provides increasing

protection against GCR.

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