The Biological Effects of Radiation in Space Radiation Effects Stochastic effects: “all or none”, can result from the effect on a single cell, e.g., cancer. Cannot predict effect on an individual basis; must use populations and risk probabilities. Deterministic effects: severity of the effect increases with increasing dose, e.g., cataracts, erythema. USAF/NASA Proton Bioeffects Project Proton energies were chosen to bracket the energies encountered in space: Proton energy Range in tissue 2 MeV 1 cm 55 MeV 2.5 cm 138 MeV ~ 15 cm 250 MeV ~ 40 cm 400 MeV ~ 80 cm 2300 MeV ~ 1000 cm ~ 2000 Rhesus monkeys ~5000 mice Image removed. USAF/NASA Proton Bioeffects Project Dose estimates in a primate head phantom. Image removed. USAF/NASA Proton Bioeffects Project All endpoints except one, indicated a proton RBE of ~ 1. Cataract formation is the exception: protons showed an LET dependency. Image removed. Carcinogenesis See [ALPEN-94] Alpen, E. L, P. Powers-Risius, S. B. Curtis, R. DeGuzman and R J. M. Fry. “Fluence-Based Relative Biological Effectiveness for Charged Particle Carcinogenesis in Mouse Harderian Gland.” Advances in Space Research 14 no. 10 (1994): 573-581. Objective: look at low doses Novel approach: Fluence versus dose Carcinogenesis Image removed. [ALPEN-94] Table 1. Carcinogenesis Mouse Harderian gland model. (secretes, tears, lubricants, hormones) Within 72 hours, 2 donor pituitary glands implanted into the spleen. Hormone production promotes the expression of Harderian gland tumors. Mice sacrificed at 16 months; Harderian glands examined macroscopically and histologically. Image removed. Graph of Dose (Gy) vs. Percent Tumor Prevalence Dose = fluence x LET Carcinogenesis Tumor incidence as a function of particle fluence. Image removed. [ALPEN-94] Fig. 2. Carcinogenesis Image removed. Table ? These are some of the highest RBE values measured in any system. ? All tumors were measured, some were benign. Carcinogenesis Cross section = the increase in proportion of animals with Harderian gland tumors per unit fluence. This is a track penumbra effect. Image removed. Fig. 14.7 in Alpen, E. L. Radiation Biophysics, 2 nd ed. San Diego, CA: Academic Press, 1998. Carcinogenesis The RBEs are significantly higher than other reports with high- LET particles. The Harderian gland RBEs never dip below 1 at high LET values. Image removed. [ALPEN-94] Fig. 3. Carcinogenesis Image removed. [ALPEN-94] Table 3. Image removed. [ALPEN-94] Table 4. Carcinogenesis Much attention has been drawn to these results. This is very troubling to NASA. Image removed. [ALPEN-94] Fig. 4. These data suggest that only a single hit by a high-LET iron particle is sufficient to cause transformation and tumor induction. Skin Cancer Incidence of skin carcinomas in rats at ~ 1 year after irradiation. Dose vs fluence? Image removed. [ALPEN-94] Fig. 6. Cataract Formation With protons, low dose rate causes less damage. Iron ions appear much more effective than x- rays for cataract induction. Image removed. [ALPEN-94] Fig. 9. Chromosome Aberrations Image removed. Premature Aging See [SHUKITT-HALE]: Shukitt-Hale, Barbara, Gemma Casadeusus, John J. McEwen, Bernard M. Rabin and James A. Joseph. “Spatial Learning and Memory Deficits Induced by Exposure to Iron-56-Particle Radiation.” Radiation Research 154 (2000): 28-33. Previous data from this group has shown: ? Exposure to 56 Fe particles disrupts behavior mediated by the dopamine neurotransmitter system. Conditioned Taste Aversion Test. ? The changes are similar to those seen in aged rats. Current study looks at cognitive function: spatial memory and learning; areas known to be affected in aging. Rats were tested at 1 month after 1.5 Gy whole-body exposure to 1 GeV/n 56 Fe. Morris Water Maze Requires rats to use spatial learning to find a hidden platform just below the surface of a pool and remember the location from the previous trial. Testing on 4 consecutive days/6 trials per day. ? Day 1: Trials 1-6; put rat into pool, measure time to find the platform and escape. ?Days 2 and 3: Trial 6; remove platform, measure time spent in quadrant where platform was previously located. Measures memory. ?Day 4: Change location of platform ?Trials 1-5; measure time to find platform and escape. ?Trial 6; remove platform, measure time spent searching in the correct quadrant. Measures learning. Morris Water Maze Image removed. [SHUKITT-HALE] Fig. 1. Premature Aging ? The escape platform has been removed. ? Measure the time spent searching in the correct location (where the platform used to be). ? Control rats are using a spatial strategy Irradiated rats are using non-spatial strategy. Image removed. [SHUKITT-HALE] Fig. 2. Premature Aging Control rats have better memory and are using spatial cues for orientation. Image removed. [SHUKITT-HALE] Fig. 4. Conclusions Whole-body irradiation with 1.5 Gy of 56 Fe 1000 MeV/n disrupted spatial memory and learning. Irradiated rats took longer to learn a new task, and forget the old one, during reversal training. Irradiated group did not use spatial strategies to find the submerged platform. Random circular swimming. Both of these are deficits similar to those seen in aged rats. X-rays can produce similar effects, but at doses of 20-30 Gy and not until 200-280 days post irradiation.