Solar and Space Physicsand the

Vision for Space Exploration

Understanding and Mitigating the Radiation Hazards of Space Travel:Progress and Future Needs

Richard B. Setlow

Senior BiophysicistBrookhaven National Laboratory

setlow@bnl.gov

Some References

1. E.L. Alpen, (1998) RADIATION BIOPHYSICS , second edition, Academic Press,

NY.

2. E.L. Alpen, et al. (1993) Tumorigenic Potential of High-Z, High-LET

Charged-Particle Radiations. Radiat. Res. 136, 382-391.

3. M.J. Bissel, panel chair (1997) “Modeling Human Risk: Cell and Molecular Biology

in Context” Laurence Berkley National Laboratory-40278.

4. F. Cucinotta, et al., (2002) “Space Radiation Cancer Risk Projections for Exploratory

Missions: Uncertainly Reduction and Mitigation”. NASA/ Technical Publication-2002-

21077

5. R.B. Setlow (1999) The U.S. National Research Council’s views of the radiation

hazards in space. Mutat.Res. 430, 169-175.

6. R.B. Setlow (2003) The hazards of space travel. EMBO reports 4, 1013-1016

Values of LET for a Range of HZE Nuclei (From Reference 4, page 8)_________________________________________________________________

Particle Type LET (keV/µm)____________________________________________

60Co 0.23

Modeling Human Risk: Cell & Molecular Biology in Context Report Number : LBNL-40278 June 1997 Mina J Bissel, Panel Chair

Calculated Value

Experimental Value

Experimental Value Experimental Value

J.RADIAT.RES., 43: SUPPL.,S1-S6 (2002)

How Do We Get from Cell and Animal Data to Risks for Humans from Space Radiations?

J.F.DICELLO

Reference 2, p.385, 386, 388

Ion Energy LET (MeV/A) (keV/um)60Co-gam 0.23Protons 250 0.4Helium 228 1.6Neon 670 25Iron 600 193Iron 350 253Niobium 600 464

.1 1 10 100 1000 LET (keV/µm)

Cross Section for Tumor Induction in Hardarian Gland in Mice Versus LET Reference 2, p.386

C

ross

Se

ctio

n (

µm2

)

100

10

1

.1

.01

.001

Cobalt-60

Protons Helium

Neon

Iron-350

Iron-600Niobium

Figure 3. Cumulative excess lifetime incidence of mammary tumours as a function of dose for the photon, proton and iron irradiated rats. At the higher doses, the likelihood of an animal surviving without at least one tumour, when the natural background rate is included, is approaching zero. Although the primary regions of interest for risk analysis are the lower dose regions, background rates and the shape of the response function at high doses was not known.

Induction of Apoptosis by Iron Nuclei or Gamma Rays

RADIATION RESEARCH 164, in press (2005)

Cytotoxic Effects of Low- and High-LET Radiation on Human Neuronal Progenitor Cells

P. Guida, M. E. Vazquez and S. Otto

FeaturesBeams of heavy ions extracted from the booster accelerator with masses and energies similar to the cosmic rays encountered in space:

• 1 billion electron volt (GeV)/nucleon iron-56• 0.3GeV/nucleon gold-97• 0.6GeV/nucleon silicon-28• 1-GeV/nucleon protons• 1-GeV/nucleon titanium• 0.29-GeV/nucleon carbon

• a new 100-meter transport tunnel and beam line to deliver the beam to a 400 square-foot shielded target hall for NASA-funded space-effects experiments

SHIELDING

Figure 6. Effects of diets A, B, D and E on the total antioxidant levels in Sprague-Dawley rats irradiated with 1 GeV/n iron ions.

1g

~0g

AN EXAMPLE OF A RECENT DETERMINATION OFRBEs

THE EFFECTS OF HZEs ON THE INDUCTION OF

GERM-CELL MUTATIONS

GERM CELL MUTATIONS IN MEDAKA FISH

[Dominant Lethals and Specific Locus Mutations]

Treated Wild Type Males are mated withHomozygous Recessive (5 color loci ) Females

Collect eggs (10-15/day) into microtiter plates

Days 1-3: treated sperm 4-9: treated spermatids ~40--- : treated spermatogonia

Score developing and hatched embryos for Dominant Lethals

andTotal and Viable Specific Locus Mutations

Proceedings of the National Academy of Sciences (2005) vol. 102, 6063-6067

Germ cell mutagenesis in medaka fish following exposures to high energycosmic ray nuclei: a human model

Atsuko Shimada*, Akihiro Shima†║, Kumie Nojima

‡, Yo Seino

† and Richard Setlow§¶

*Department of Biological Sciences, School of Sciences, † University of Tokyo, Department ofIntegrated Biosciences 102, Graduate School of Frontier Sciences, University of Tokyo,‡International Space Radiation Laboratory, National Institute of Radiological Sciences, Chiba,§Biology Department, Brookhaven National Laboratory, Upton, NY 11973-5000

Contributed by Richard Setlow

¶To whom correspondence should be addressed. E-mail: setlow@bnl.gov

Classification: Biological Sciences, Genetics

Dose Response Data

sperm

tids

gonia

Table 3. Relative Biological Effectiveness (± SD) of HZE Nuclei Induction of Mutations in Sperm, Spermatids (tids) and Spermatogonia (gonia)

3.5 GeV12

C 56 GeV 56

Fe sperm DL 1.32 ± 0.13 1.49 ± .020 TM 1.69 ± 0.29 1.89 ± 0.20

tids DL 1.54 ± 0.10 2.00 ± 0.23 TM 2.1 ± 0.5 2.94 ± 0.47

gonia DL 5.4 ± 1.0 6 ± 8 TM 1.0 ± 1.4 1.7 ± 1.2

CONCLUSIONS

1. The RBE values for germ-cell mutations are ~10-foldless than those for cancer induction or thekilling/mutation of somatic cells.

2. The numbers of viable mutations from all exposedstages are very low and would not yield significantmutation frequencies.

3. Total mutations from exposed spermatogonia showbarely significant increases above control levels.

4. Damaged stem cells probably undergo apoptosis orresult in abnormal sperm that would yield dominantlethals.

5. The hazard to exposed human males is probablytemporary sterility, but no significant mutagenic effects.