Effects of Radiation Exposure on Humans

The quality factor has originally been developed for radiation protection purposes. Therefore it is mainly based on radiation risks for cancer induction in mammals. The effects of radiation exposure on humans can be grouped into two basic categories: acute effects or delayed effects. Acute effects usually appear quite soon after exposure when people receive high

5 Figure 7-04 shows the percent contribution from the different ions of GCR to the dose equivalent.

doses in a short period of time (minutes to a few hours). Delayed effects, such as cancer, can occur when the combined dose and dose rate are too small to cause acute effects leading to death or early morbidity6.

The Acute Radiation Syndrome (ARS) is a sequence of phased symptoms which vary with individual radiation sensitivity, type of radiation, and the radiation dose absorbed. After radiation exposure with doses well above 1 Sv, the ARS is characterized by the rapid onset of nausea, vomiting, and malaise, which is followed by a nearly symptom free phase of weeks to days, depending on dose. Humans who have received doses of radiation between 0.7 and 4 Sv will have depression of bone-marrow function, known as the hematopoietic syndrome. This syndrome leads to decreased resistance to infections from lymphocyte deprivation and anemia within 2-6 weeks and death from sepsis. Death rate for this syndrome peaks at 30 days after exposure, but continues out to 60 days. Higher single doses of ionizing radiation (6-8 Sv) will result in a gastrointestinal syndrome, including severe fluid losses, hemorrhage, and diarrhea, starting after a short latent period of a few days to a week. Derangement of the luminal epithelium and injury to the fine vasculature of the sub mucosa lead to loss of intestinal mucosa. Without treatment, radiation enteropathy consequently results in an inflammatory response upon infection by bacterial transmigration. Deaths from sepsis may occur between 3 and 10 days post exposure. After radiation with very high acute doses (20-40 Sv) and a very short latent period from several hours to 1 to 3 days, the clinical picture is of a steadily deteriorating state of consciousness with eventual coma and death (neurovascular syndrome). Symptoms include loss of coordination, confusion, convulsions, shock, and the symptoms of the blood forming organ and gastrointestinal tract syndromes, survivors cannot be expected.

The Chronic Radiation Syndrome (CRS) was defined as a complex clinical syndrome occurring as a result of the long-term exposure to total radiation doses that regularly exceed the permissible occupational dose by far (2-4 Sv/year). Clinical symptoms are diffuse and may include sleep and/or appetite disturbances, generalized weakness and easy fatigability, increased excitability, loss of concentration, impaired memory, mood changes, headaches, bone pain, and hot flashes. The severity of delayed effects depends on dose. These delayed effects may include cancer, cataracts, non-malignant skin damage, death of non-regenerative cells/tissue, genetic damage, impact on fertility, and suppression of immune functions.

For radiation doses <1 Sv per year the induction of tumors is the most important long-term secondary disorder. Tumor induction with low doses is considered to occur stochastically, that means as a consequence based on statistical probability. Nevertheless, most of the data used to construct risk

6 Morbidity is a disease, condition or state.

estimates are taken from radiation doses greater than 1 Sv and then extrapolated down for low-dose probability estimates. Significant direct data are not available for absolute risk determination of doses less than 0.1 Sv. In the case of the various radiation-induced cancers seen in humans, the latency period may be several years up to 2-3 decades. It is difficult to address the radiation-induced cancer risk on Earth of an individual person due to the already high background risk of developing cancer. Even less is known on cancer risk from complex space radiation.


The accessibility of the unique radiation environment in space and the increasing involvement of human beings in space missions have initiated space activities in fields of radiobiological research as follows:

a. Biological mechanisms of cosmic ray heavy ions, the so-called HZE particles;

b. Impact of spaceflight environment on biological radiation response;

c. Radiation dosimetry;

d. Radiation protection issues.

The results of these studies are discussed in the following sections.

4.1 Biological Effects of HZE Particles

To understand the ways by which single particles of cosmic radiation interact with biological systems, methods have been developed to precisely localize the trajectory of an HZE particle relative to the biological object and to correlate the physical data of the particle relative to the observed biological effects along its path.

Such effect-particle correlations were accomplished in spaceflight experiments in different ways:

a. By use of visual track detectors that were sandwiched between layers of either biological objects in resting state, like viruses, bacterial spores, plant seeds or shrimp cysts, or embryonic systems, like insect eggs, realized in the so-called Biostack concept (Figure 7-10) (Biicker and Horneck 1975);

b. By use of nuclear track detectors that were in fixed orientation to biological targets of interest, like implantations beneath the scalp of animals or helmet devices for astronauts (see Kiefer et al. 1996 for review);

c. By correlating the occurrence of radiation effects, like the light flash phenomenon, with orbital parameters, such as passages through the SAA of the radiation belts.

The results from experiments in space investigating the radiobiological importance of the HZE particles of cosmic radiation are summarized by Horneck (1992), Swenberg et al. (1993), and Kiefer et al. (1996). The major findings are discussed below.

4.1.1 Effects on Biological Systems in Resting State

The need for experimental methods to localize each penetrating HZE particle and to determine its relationship to potential biological effects along its path, so far, has been accomplished in experiments on biological systems in resting state. For that purpose, monolayers of selected biological objects, fixed in position, were sandwiched between visual nuclear track detectors (Figure 7-10). Post flight analysis comprised steps as follows:

a. Localization of each HZE particle's trajectory in relation to the biological specimens;

b. Separate investigation of the response of each biological individual hit, in regard to radiation effects;

c. Determination of the impact parameter (i.e., the distance between particle track and sensitive target);

d. Determination of the physical parameters (Z, E, LET) of the relevant HZE particles;

e. Correlation of the biological effect with the HZE particle parameters.

Figure 7-10. The Biostack concept to localize biological effects produced by single HZE particles of cosmic radiation. Biostack experiments were flown on board Apollo-16, -17, ASTP, Spacelab-1, Dl, IML-1, IML-2, LDEF, Cosmos-1887 and-2004, and EURECA missions.

The biological systems investigated, all of them being in resting state, were characterized by a long shelf life. They had to endure fixed arrangement between the track detectors and relatively long pre- and post flight storage periods. A large variety of biological specimens, such as bacteriophages, bacterial spores, plant seeds, and animal cysts allowed the evaluation of radiation effects at different levels of biological organization. These specimens possessed different radiation sensitivities (as known from radiobiological experiments with X-rays, y-rays, or electrons), and they consisted of either replaceable or non-replaceable cells, or embryonic tissue, respectively. Sandwiches of this type of combination of biological layers and nuclear track detectors were flown on several space missions (see Horneclc 1992 for review).

In bacteriophage T4, placed in thin films between plastic track detectors during the ASTP mission, the mutation frequency was increased by a factor of 14 in areas traversed by an HZE particle compared to ground controls. The majority of genetic changes (65%) consisted of small deletions, insertions, inversions, elongated deletions, or multiple lesions, respectively, which let suggest DNA strand breaks to be the primary radiation damage.

The responses of a single microbial cell to the passage of a single HZE particle of cosmic radiation were studied on spores of the bacterium Bacillus subtilis in the Biostack experiments (reviewed in Nicholson et al. 2000). Figure 7-11 shows the frequency of inactivated spores as a function of the distance from the particle track, the impact parameter b. About 1000 individual spores were analyzed. Spores within b < 0.25 (im were inactivated by 73%. The frequency of inactivated spores dropped abruptly at b > 0.25 jim. However, 15-30% of spores located within 0.25 < b < 3.8 |xm were still inactivated. Hence, spores were inactivated well beyond 1 (rm, which distance would roughly correspond to the dimensions of a spore. At the distance of 1 (rm, the mean 5-ray (secondary electrons) dose ranged between 0.1 Gy and 1 Gy, depending on the particle, and declines rapidly with increasing b (Facius et al. 1978, 1994). This value of 0.1 to 1 Gy is by several orders of magnitude below the D0 (dose reducing survival by e"1) of electrons, which amounts to 550 Gy (see also Figure 7-08). Therefore, the radial long-ranging effect around the trajectory of an HZE particle (up to b = 3.8 (im) cannot merely be explained by the 8-ray dose.

These results were largely confirmed by experiments at heavy ion accelerators using single ions (Weisbrod et al. 1992). Taking the results from the experiments in space as well as those obtained at accelerators, one can draw the following general conclusions:

a. The inactivation probability for spores, centrally hit, is always substantially less than one;

b. The effective range of inactivation extends far beyond the range of impact parameter where inactivation of spores by 8-rays can be expected. This far-reaching effect is less pronounced for ions of low energies (1.4 MeV/u), a phenomenon which might reflect the "thindown effect" at the end of the ion's path; c. The dependence of inactivated spores from impact parameter points to a superposition of two different inactivation mechanisms: a short ranged component reaching up to about 1 pm may be traced back to the 8-ray dose and a long-ranged one that extends at least to somewhere between 4 and 5 pm off the particle's trajectory, for which additional mechanisms are conjectured, such as shock waves, UV radiation, or thermophysical events (Facius et al. 1978).

I I I i r;""; ; ;"•;•• i [■-■■■■■■■■

Bios tack / HZE- \ Etching Micro Incubiifion with spores particles manipuïatioii

Imjiact Parameter (pin)


Figure 7-11. Percentage of inactivation of Bacillus subtilis spores by single HZE particles (Z>12, LET>200 keV/fjm) of cosmic radiation as a function of the impact parameter. Results of the Biostack experiment flown on board the Apollo-Sovuz Test Project (ASTP). Adapted from Horneck (1992).

With plant seeds that were exposed to cosmic HZE particles when in fixed contact with track detectors, methods were developed to determine the impact parameter of the most sensitive target, i.e., the meristem of root or shoot (Figure 7-12).

In seeds of Arabidopsis thaliana or Nicotiana tabaccum, hit by an HZE particle, development is significantly disturbed, as demonstrated by loss of germination (early lethality) or embryo lethality. Seeds of impact parameters b<120 urn related to their shoot meristem were inactivated to 90%. In addition, seedling abnormalities, such as hypertrophy or deformation of cotyledones, hypocotyls, or root, or chlorophyll deficiency occurred with high frequency as a consequence of a passage of a single HZE particle close to the shoot or root meristem. Evidently, these severe impairments were based on irreparable damage to the genetic apparatus, as demonstrated by the high frequency of multiple chromosomal aberrations developed in Lactuce sativa seeds hit by an HZE particle.

Among Zea mays seeds flown on the Apollo-Soyuz Test Project (ASTP), one seed that received 2 hits by HZE particles (Z>20, LET = 100150 keV/jxm) in the central region of the embryo developed a somatic mutation, as evidenced by large yellow strips in all leaves. The extent of this mutation had never been observed before, neither in flight nor in ground experiments.

Among animal resting systems, the mosaic egg of the brine shrimp Artemia salina resting in encysted blastula or gastrula state represents an investigative system that, during further development, proceeds to the larval state, the free swimming nauplius, without any further cell division. Therefore, injury to single cells of the cyst will be manifested in the larva. A wealth of data has been compiled on the response of this encysted embryonic system to single HZE particle hits from a series of spaceflight experiments outside the geomagnetic shielding (Apollo-16 and -17) or in LEO (Biostack on ASTP, Biobloc on Cosmos-782, -1129, -1887 or Salyut-7). It was clearly demonstrated that the passage of a single HZE particle through a shrimp cyst damages a cellular area large enough to disturb either embryogenesis or further development or integrity of the adult.

Emergence, characterized by bursting of the eggshell and appearance of the nauplius larva still enclosed in a membrane, was slightly disturbed by an HZE particle hit. The subsequent step of hatching, characterized by release of a free-swimming nauplius, was severely inhibited by an HZE particle hit. From the lunar and ASTP missions, an approximately 90% loss of hatching was reported (Buclcer, 1975). Whereas, after the ASTP mission, a high lethality was noticed during the days following hatching, this effect was less expressed after the Cosmos or Salyut missions. Additional late effects, due to a hit of a single HZE particle, were delay of growth and of sexual maturity, and reduced fertility. In the Biostack experiments, not a single nauplius larva that developed from a cyst hit was normal in further growth and behaviour. Anomalies of the body or extremities appeared approximately ten times more frequently than in the ground controls.

Figure 7-12. Biostack method used to determine the impact parameter for the most sensitive target in plant seeds after exposure to HZE particles of cosmic radiation.

Figure 7-12. Biostack method used to determine the impact parameter for the most sensitive target in plant seeds after exposure to HZE particles of cosmic radiation.

4.1.2 Effects on Developing Embryonic Systems

As animal embryonic systems, eggs of the beetle Tribolium confusum and of the stick insect Carausius morosus were studied in relation to a hit by a cosmic HZE particle. The development of larvae of Tribolium confusum up to the pupal state was severely hampered. The frequency of malformations, such as curved abdomen, fused segments of the abdomen or antenna, split or shortened elytra, was approximately 20 times higher than in the ground control. Likewise, hatching of the Indian stick insect Carausius morosus from eggs hit by a cosmic HZE particle was significantly reduced. Malformations were increased in individuals having developed from eggs hit. They are characterized by curved abdomina, fused segments, or shortened legs.

In summary, evaluation of the effects observed in bacterial spores, in plant seeds, and animal embryos demonstrated that single HZE particles induce significant biological perturbations in all these test organisms, although with varying efficiency. The observed effects comprise gross somatic mutations, severe morphological anomalies, disturbance of development, or complete inactivation. From biophysical analysis of some of these results, it was concluded that the magnitude of these effects could not be explained in terms of established mechanisms and, in particular, that the lateral extension of effectiveness around the trajectories of single particles exceeds the range, where secondary electrons could be considered to be effective.

With most embryonic systems investigated so far, a reduced vitality was also observed in the flight non-hit specimens compared to controls on ground. This effect might be caused by additional spaceflight parameters, such as cosmic ray events which are microdosimetric, similar to HZE particles, such as stars of nuclear disintegration. Other parameters include cosmic background radiation and microgravity, which affect the integrity of the biological organisms in space individually or in combination. This phenomenon will be discussed in Section 4.2.

4.1.3 Effects in Mammals

First qualitative evidence of tissue damage produced by cosmic ray HZE particles in the skin of mice was given in 1956 by Chase and Post (cited in Horneck 1992). After high altitude balloon flight exposures, the animals developed segments of white hair. The number of white areas could roughly be related to the number of HZE particle hits.

In the retina of rats, exposed for 19 days to cosmic ray HZE particles during the high inclination (62.8 deg) flight of Cosmos-782, necrotic nuclei and channels of lengths up to 26 jim were detected. Their number was in agreement with the number of HZE particles received during that flight. Comparable lesions were produced by Ne or Ar ions in accelerators. During the subsequent Cosmos-936 biosatellite mission equipped with an onboard 1-g reference centrifuge, rats in 1 g in space developed morphological alterations in their retina that were comparable in number, type, and size to those from animals kept in microgravity. Although tracking of the HZE particles in the tissue were not studied in these experiments, all observations point to HZE particles as the cause of the channels and cellular alterations observed in the rats' retina (Philpott et al. 1980).

In rats flown on board Spacelab-3, the loss of spermatogonia in the testes was used as a biological dosimeter. Whereas only 0.5% loss of spermatogonia was expected from the radiation dose received, a 7% loss was detected. This increased loss of spermatogonia might be caused by a combined action of HZE particles and of other factors prevailing during spaceflight, such as background radiation, microgravity, or stress.

4.1.4 Light Flash Phenomenon

The problem of potential hazard to astronauts from cosmic ray HZE particles became "visible" when the astronauts of the Apollo-11 mission reported light flashes, i.e., faint spots and flashes of light at a frequency of 1 or 2 per minute after some period of dark adaptation. These events were observed during translunar coast, in lunar orbit, on the lunar surface, and during transearth coast. Evidently, these light flashes that were predicted by Tobias in 1952, result from HZE particles of cosmic radiation penetrating the spacecraft structure and the astronaut's eyes, and producing visual sensations through interaction with the retina.

Systematic investigations were then performed during the following six Apollo missions that carried the spacecraft outside the magnetic shielding of the Earth, during the Apollo-Soyuz Test Project (ASTP) in LEO, as well as inside ground-based accelerators. These studies demonstrated a variety of different types of flashes, such as thin short or long streaks, double streaks, star like flashes or diffuse clouds, respectively, that were white in general. However, the pattern of types of flashes was different in LEO, in lunar missions, or in accelerators.

A helmet-like device with nuclear emulsions was used by the crew of Apollo-16 and -17 in order to record the passage of HZE particles through the astronaut's head and eyes and to correlate them with observed light flashes. This Apollo Light Flash Moving Emulsion Detector (ALFMED) consisted of two sets of glass plates coated with nuclear emulsions. One set was fixed in position, whereas the second parallel located set was moved at a constant rate of 10 Lun/s for a total translation time of 60 min. Only in a few cases the passage of an HZE particle through the astronaut's eyes coincided with a light flash event. However, the number of HZE particles traversing the eyes of the astronaut during the translation period agreed with the total number of flashes observed during this period.

Investigations on the frequency of visual light flashes in LEO and its dependence on orbital parameters were performed on Skylab-4, ASTP, and Mir. The highest light flash rates were recorded when passing through the SAA. In this part of the orbit, the inner fringes of the inner radiation belts come down to the altitude of LEO, which results in a 1000 times higher proton flux than in other parts of the orbit. These high light flash event rates during the SAA passages can be deduced either to the high proton fluxes or to the occurrence of some particles heavier than protons in the inner belts of trapped radiation. Casolino et al. (2003) identified two separate mechanisms for the induction of light flashes with the SILEY experiments on board Mir. The first mechanism is a direct interaction of heavy ions with the retina causing excitation or ionization. The second mechanism results from proton-induced nuclear interactions in the eye (with a lower interaction probability) producing knock-out particles. Stimulation of the retina could be caused be electronic excitation resulting in UV radiation in the vicinity of the retina, ionization in a confined region associated with S-rays around the track, or shock wave phenomena when HZE particles pass through the tissue matrix.

4.1.5 Effects on the Central Nervous System

The light flash phenomenon gives an example that HZE particle hits are "seen" by the astronaut. The question arises what happens to the other organs or tissues of the body exposed to cosmic radiation. Of special concern is the Central Nervous System (CNS) where the damage to relatively small groups of cells that cannot replace themselves may result in severe physiological effects.

Tracks of necrotic cells were detected in the brain of balloon-borne monkeys. These tracks were interpreted to be caused by the passage of single heavy ions of cosmic radiation. In order to correlate potential brain damage with the traversal of cosmic ray HZE particles, nuclear track detectors were implanted beneath the scalp of mice during the Apollo-17 mission in the experiment Biocore. Five pocket mice with subscalp dosimeters were exposed to cosmic radiation. Electron microscopic observations did not detect any lesions in the brain or retina that could be attributed to the passage of an HZE particle. This absence of demonstrable lesions might be due to the highly shielded location of the experiment inside the spacecraft resulting in a very low particle flux.

However, lesions were detected in the epidermis and in hair follicles on the scalp of the animals, characterized by necrotic epithelia cells and leukocytes. Only in one case, a coincidence between a lesion and a registered particle could be established. Since the tissue exhibited chronic inflammation attributable to the presence of the dosimeters, it remains uncertain whether the residual lesions were really produced by yet unregistered HZE particles, or whether they were just an experiment-dependent artifact. Hence, the issue whether cosmic ray HZE particles produce microscopically visible injury in the brain needs further consideration.

4.1.6 Chromosomal Aberrations

An elevation of the frequencies of chromosomal aberrations in peripheral lymphocytes has been reported in astronauts after long-term space flights. Obe et al. (1997) investigated lymphocytes of seven astronauts that had spent several months on board the Mir space station. They showed that the frequency of dicentric chromosomes increased by a factor of approximately 3.5 compared to preflight control.

The observed frequencies agreed quite well with the expected values based on the absorbed doses and particle fluxes encountered by individual astronauts during the mission. These data suggest the feasibility of using chromosomal aberrations as a biological dosimeter for monitoring radiation exposure of astronauts.

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