Space Radiation Health Effects of Astronauts in Explorative Missions Günther Reitz Radiation Biology Department Institute of Aerospace Medicine German Aerospace Center (DLR)

‘Fault tree’ of Fatal event The most harmful environmental factors are Cosmic ionizing radiation and secondary radiations produced by interaction of the cosmic primaries with atoms and molecules of the atmosphere or shielding material as well as the human body itself Solar particle events that occur sporadically and may last over several days, which cause temporally substantial increases in the radiation dose Reduced gravity of 0.377  g which is experienced by the crew after a trip in microgravity for nearly one year and a heavy g-load up to 6 g during landing 2

Fluxes of primary space radiation components inner Van Allen belt protons

Effective Doses Low Earth Orbit Missions and Missions to the Moon

GCR exposure in interplanetary space BON2011/BON2010≈ 1.35 BON2011/DLR ≈ 1.1 DLR BON2010 BON2011

Worst$ case' SPE radiation exposures in Sv during different mission phases for critical tissues under different mass shielding

Limits for Astronauts in LEO (NASA as example) Career non-cancer and Short term effects Career cancer risk limits Dose (Gy-Eq) BFO Eye Skin Career NA 4.0 Annual 0.5 2.0 3.0 30 days 0.25 1.0 1.5 Effective Dose (Sv) Age Male Female 25 0.7 0.4 35 1 0.6 45 1.5 0.9 55 3 1.7 For reference: Limits for radiation workers on Earth: 20 mSv annual and 400 mSv career

How Astronauts are Affected by Cosmic Rays?

DNA is the MainTarget of Radiation Action Energy deposition DNA damage Cell cycle arrest Repair Cellular Survival Clonal Expansion Transformation Mis-repair Mutations Carcinogenesis Cell death, e.g. by Apoptosis Misdifferentiation Senescence No repair biological effects of radiation are a consequence of chemical reactions initiated by energy deposition in cells and tissues these reactions modify the division processes by which cells reproduce as well as other cell functions required for healthy living organisms cells repair themselves; when that repair is successful, the tissues and organisms return to their normal state, when repair is not successful, cells may die tissue integrity and function may be impaired, as occurs in acute radiation effects repair may be successful from the point of view of cell survival, but may contain latent errors that only manifest in subsequent generations of dividing cells DNA lesions depend in type and quantity on the quality and dose of radiation radiation-induced DNA damage affects cellular reproducibility and conservation of genetic stability Resulting in cellular inactivation and mutation induction cells have developed pathways to detect, signal and repair DNA damage altered expression of regulatory proteins represent important early events in the process of oncogenic transformation compensatory mechanisms exist, such as apoptosis, protein expression and processing, and signal transduction modulation of gene expression is mediated by promoter specific interactions and regulatory elements like transcription factors The cell-protective and cell-destructive responses to DNA damage are downstream of a common signal transduction network that has been studied intensively in recent years. While most protein components of this signaling network have been identified, the current knowledge does not explain when and why a damaged cell will choose to die. In other words, we have not yet elucidated the rules that govern the cell death response to DNA damage. Biological effects of radiation Consequence of chemical reactions initiated by energy deposition in cells and tissues Involve DNA damage recognition, repair, and induction of signalling cascades leading to cell cycle checkpoint activation, apoptosis, and stress related responses Nuclear factor kB (NF-kB) is activated as a part of the DNA damage response and is thought to orchestrate a cell survival pathway Is essential for maintenance of genome stability and avoiding the passage to neoplasia Cellular Response to radiation is complex and relies on simultaneous activation of different networks. It involves DNA damage recognition, repair, and induction of signalling cascades leading to cell cycle checkpoint activation, apoptosis, and stress related responses. The fate of damaged cells depends on the balance between pro-and antiapoptotic signals. In this decisive life or death choice, the transcription factor NF-kB has emerged as a prosurvival actor in most cell types. As corollary, it appears to be associated with tumorigenic process and resistance to therapeutic strategies as it protects cancerous cells from death. Nuclear factor kB (NF-kB) is activated as a part of the DNA damage response and is thought to orchestrate a cell survival pathway, which, together with the activation of cell cycle checkpoints and DNA repair, allows the cells in cases of limited damage to restore a normal life cycle unharmed. 9 9

Radiation Effects

Early morbidity/mortality for worst case SPE behind 10 gm/cm2 in interplanetary space

How Real are Radiation Risks for Astronauts from SPEs ? Radiation dose to astronauts from solar events during the Apollo era missions The August 1972 event, just between Apollo 16 and 17 missions) reached doses up to 30 Gy (LD50/30 = 3.5 Gy, 50 % lethality within 30 days) 12

Uncertainties in Radiation Risk Projection Risk Projections 10% Maximum Acceptable Risk Mars ▲ 1% ▲ ISS Mission SPE?? Lunar 0.1% ▲ 95% Confidence Interval “95% Confidence Interval” Shuttle Mission ▲ 0.01% Individual’s Fatal Risk Point Estimate

Major sources of uncertainty of risk estimation from space radiation field

Radiation Risk in a 550 day mission to Mars Cucinotta (Space Radiation Risk Calculation) 45 Year old male, US Population, 20g/cm^2 shielding Aug 72 Solar Particle event, 340 mSv REID 0.98 % (0,23;2.59) 550 day Mission to Mars GCR ,550 mSv) REID 2.00 % (0.33;5.01) ICRP 550 day mission Excess Risk/Sv 4x 10^-2 results in 3.6%

Significance of Shielding Material for GCR (20g/cm^2 shielding, 40-yr males)

Light Light Flash Observations

Observation of Cataracts RBE ~ 200 !! F. A. Cucinotta et al., 2001

Countermeasures against radiation effects develop proper risk criterion for exploratory LONG term missions integrate radiation risk assessment into total risk analysis reduce uncertainties for exposure estimates reduce uncertainties for dose effect relations (late & early) Improve advance risk assessment optimise shielding design, include storm shelters (material & thickness ) optimise mission design duration timeline relative to solar activity cycle guarantied shelter accessibility advance forecasting capabilities for solar particle events monitor and document exposure history and health status Minimise radiation exposure select genetically resistant individuals modify dose response curve of ‘normal’ crew members attenuate early effects by prior and post medication mitigate late effects by prophylactic nutrition Maximise radiation resistance

Radiation Assessment Detector (Cruise Measurements) SPE Exposures mSv 23-29 Jan 4 7-15 March 19.5 17-18 May 1.2 GCR Exposure/day 1.8

Conclusions GCR Risks SPE Risks Stochastic effects such as cancer induction and mortality or late deterministic effects, such as cataracts or damage to the central nervous systems are of concern Doses present no acute health effects in deep space missions There are no data for human exposures to these radiation to estimate risks of astronauts Usual methods of estimating risk by calculating dose equivalent or equivalent dose are questionable to be appropriate for these particles Upper 95% C.I. for excess cancer risks from GCR for an mission to Mars may exceed current limits defined for Low Earth Orbits During interplanetary cruise shielding is limited and will therefore not significantly reduce GCR risks SPE Risks Risks are manageable by shielding measures Shielding should limit excessive exposure to prevent acute effects Hydrocarbon shields offer a reduction of a factor of two compared to Aluminium Exploration vehicles shielding should focus on SPE instead on GCR

SPARES

Solar corona and sudden release of a huge clouds of particles

Excess Relative Risk as a function of rate of exposure Gregoire O. et.al., Radiat. Biol., 2006

Excess Relative Risk as function of dose rate

Fatal Cancer Risks near Solar Minimum (20 g/cm^2 shielding) Slide Courtesy of F. A. Cucinotta

Fatal Cancer Risk Near Solar Maximum (PHI=1100MV including 1972 SEP) Slide Courtesy F. A. Cucinotta