Electron radiation was used to simulate the total doses, patterns of dose distribution and dose rates for an SPE. In the skin, exposure to simulated SPE radiation using 6 MeV electrons at doses up to 25 Gy causes hyperpigmentation, excessive desquamation and histopathological changes in pigmented skin. The hyperpigmentation observed was shown histologically to be the result of increased melanin deposition in the epidermis. Previous studies have also shown increased pigmentation to be connected to dermal or epidermal deposition of melanin, whereas sham-irradiated, pigmented pigs do not demonstrate melanin in the dermis (5
). The time postirradiation until the appearance of hyperpigmentation did not appear to be affected by dose in previous studies (5
) or in this study. A range of times until the onset of clinical signs in the skin has been reported, suggesting that the time to onset is not related to dose and radiation quality (5
). Approximately 10% of humans exposed to a skin dose of 22–52 Gy of megavoltage radiotherapy experience erythema, tanning (or hyperpigmentation) and desquamation (11
). Due to the use of light gray pigs in this study, it was difficult to assess the degree of erythema that may have been present after irradiation. Other studies that have used both pigmented and unpigmented pigs have also found that erythema could not be evaluated in the pigmented pigs, although sufficiently high doses of radiation caused erythema to the skin of white pigs (5
). The histolopathological changes (pigment incontinence and keratinocyte necrosis) observed in the biopsies have also been observed in human patients who experienced radiation dermatitis after fluoroscopic radiation overdose (12
The skin toxicity observations reported here are consistent with previous studies describing the acute response of human and porcine skin to these doses. For example, humans exposed to fluoroscopy at doses greater than 2 Gy have developed erythema and epilation of the skin, with desquamation also observed at skin doses between 10 and 15 Gy (13
). Irradiating pigs with a single dose of 250 kV X rays resulted in an ED50
for early moist desquamation of approximately 27.26 Gy (6
). In this study, it also appears that doses greater than 20 Gy may cause a loss of skin integrity, resulting in blistering and ulceration. These lesions may be painful and could become infected, which could be detrimental to an astronaut during a mission. It has been found that astronauts returning from space have an increased coarsening of the skin (characterized by a decreased hydration of the stratum corneum) that is consistent with astronauts’ complaints of skin pruritis and dryness (14
). In these studies, skin dryness and pruritis were found in animals exposed to electron radiation.
Pigs serve as a model for the study of radiation effects on the lungs because their lungs are anatomically and physiologically similar to human lungs. In addition, due to their size, they are a practical laboratory animal model (15
). In this study, doses from 7.5 Gy to 25 Gy resulted in significant toxicity to internal organ systems, with pulmonary toxicities being most pronounced. One of three animals irradiated with 7.5 Gy, one of three animals irradiated with 12.5 Gy, and all three animals irradiated with 25 Gy experienced a radiation-associated pneumonopathy with a radiographic pattern that followed the pattern of dose deposition. Animals that received 7.5 to 25 Gy also experienced immunological dysfunction as seen in the increased DTH response to PHA and subsequent mycoplasmal infection in the animals treated with 25 Gy. Although the decreased DTH response and the mycoplasmal infection may have been due to an immunological dysfunction created by the exposure to radiation, in the animals that were found to have pneumonia, the decreased DTH response may also have been attributable to the secondary mycoplasmal infection. Further investigation is necessary to determine the exact cause for the immunological dysfunction. Since the majority of animals that developed pneumonia were in the highest dose group, it is speculated that it was actually the exposure to radiation itself that caused the immunological dysfunction. The stress associated with the irradiation procedure is not believed to be the cause because all animals underwent the exact same procedure, but clinical signs developed quickly and most aggressively in the animals that had received the highest dose (25 Gy) of radiation.
is a widespread and endemic microbial agent found in most swine herds. It can be present within a swine population at undetectable levels for an extended period and generally results in a subclinical or uncomplicated infection except when other infectious agents or stressors are present that increase the susceptibility to disease. It is rarely seen clinically in the laboratory animal environment. M. hyopneumoniae
colonizes the airway of any age pig, generally causing a mild disease displayed by coughing, dyspnea and fever (16
). In the case of the animals in this study, it is speculated that radiation caused an immunological dysfunction and pulmonary pathology, resulting in increased susceptibility to infection with M. hyopneumoniae
. The pulmonary pathology observed radiographically and histologically was consistent with the lesions observed in humans diagnosed with radiation pneumonitis (i.e., ground glass opacities on CT scan, edema, inflammatory cell accumulation, pleural thickening and fibrosis on histology), with some features also consistent with M. hyopneumoniae
infection (i.e., cranioventral lung consolidation on necropsy, bronchointerstitial pneumonia on histology) (15
). Functional lung damage in pigs likely occurs after a threshold volume of lung is exposed to radiation (19
). It appears that a cooperative effect between the highly inhomogeneous dose distribution and immunological dysfunction may have led to pulmonary toxicities that occur in a shorter time after irradiation and at a much lower mean lung dose than has been reported previously (15
). These experiments, along with the results for humans irradiated in clinical trials using inhomogeneous irradiation fields (20
), suggest that pneumonitis could be the result of a combination of high doses to a small portion of the lung along with low radiation doses to a large volume of the lung.
The neurological signs seen in one of three pigs exposed to 25 Gy may have been related to central nervous system toxicity, which has been described in humans after radiation therapy (i.e. lethargy, ataxia, lower-extremity weakness and hyperreflexia) (17
). In humans, radiation myelopathy is typically a late complication, occurring 9 to 15 months after radiation therapy (17
). This effect may also be related to the highly inhomogeneous dose distribution delivered to the animals.
The effects observed in WBC, lymphocyte and neutrophil counts are likely due to both primary and secondary radiation effects. At 24 h postirradiation the effects on blood cell counts are likely to be due to the cell killing effects of radiation. However, some of the other effects observed in WBC at later times may be due to both primary and secondary radiation effects. For example, the elevation of WBC counts at 30 days after exposure to 25 Gy may be evidence of mycobacterial infection occurring in the third and fourth weeks postirradiation, which is suggestive, although not definitively diagnostic, of a clinical picture in which radiation pneumonitis is followed by a superinfection with mycoplasmal pneumonia. Thus the significant elevation in WBC count at day 30 in the group of pigs irradiated with 25 Gy was associated with superinfection that occurred at that time and also represents a secondary, radiation-associated WBC alteration. In conclusion, using total doses, doses rates and patterns of dose distribution that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities to both superficial and deep organs. Further research is necessary to determine whether SPE-like proton radiation will cause similar or even greater toxicity to the skin and internal organs. Finally, these effects model a relatively superficial SPE. It is predicted, however, that more severe effects may occur after exposure to a “harder” SPE because of the increased amount of radiation dose received in deeper tissues compared to the current model of 6 MeV electrons, which is equivalent to the dose–depth characteristics of 50 MeV protons.