Nonstochastic effects of different energy beta emitters on pig skin

Circular areas of pig skin from 1- to 40-mm diameter were irradiated with beta emitters of high, medium, and low energies, 90Sr, 170Tm, and 147Pm, respectively. The study provides information for radiological protection problems of localized skin exposures. During the first 16 weeks after irradiation 90Sr produced a first reaction due to epithelial cell death followed by a second reaction attributable to damage to the dermal blood vessels. 170Tm and 147Pm produced the epithelial reaction only. The epithelial dose response varied as a function of beta energy. The doses required to produce moist desquamation in 50% of 15- to 22.5-mm fields (ED50) were 30-45 Gy from 90Sr, approximately 80 Gy from 170Tm, and approximately 500 Gy from 147Pm. A model involving different methods of epithelial repopulation is proposed to explain this finding. An area effect was observed in the epithelial response to 90Sr irradiation. The ED50 for moist desquamation ranged from approximately 25 Gy for a 40-mm source to approximately 450 Gy for a 1-mm source. The 5-, 9-, and 19-mm 170Tm sources all produced an ED50 of approximately 80 Gy, while the value for the 2-mm source was approximately 250 Gy. It is also suggested that the area effects could be explained by different modes of epithelial repopulation after irradiation. After high energy beta irradiation repopulation would be mainly from the field periphery, while after lower energy irradiation repopulation from hair follicle epithelium would predominate.     

Time- and dose-related changes in the thickness of skin in the pig after irradiation with single doses of thulium-170 beta particles

Time-related changes in skin thickness have been evaluated in the pig using a noninvasive ultrasound technique after exposure to a range of single doses of 0.97 MeV beta particles from (170)Tm plaques. The reduction in relative skin thickness developed in two phases; the separation into two phases was statistically justified only after 120 Gy (P = 0.04). The first phase was between 12 weeks and 24 weeks after irradiation. No further changes were seen until 48-60 weeks after irradiation, when a second phase of skin thinning was observed. No further changes in relative skin thickness were seen in the follow-up period of 104 weeks. The timing of these phases of relative skin thinning was totally independent of the radiation dose; however, the severity of each phase of radiation-induced skin thinning was related to the dose. The pattern of changes was similar to that reported previously after irradiation with 2.27 MeV beta particles from (90)Sr/(90)Y, but the degree of dermal thinning was less for a similar skin surface dose. From a comparison of the depth-dose distribution of the beta particles from the two radionuclides, it was concluded that the target cell population responsible for both the first and second phase of skin thinning in pig skin after irradiation may be located at approximately 800 microm depth. This corresponds to an area in the reticular dermis in pig skin and may be the appropriate site at which to measure the average dose to the dermal tissue.     

Late occurring lesions in the skin of rats after repeated doses of X-rays

Late radiation damage, characterized by atrophy and necrosis in the skin and subcutaneous tissues, has been demonstrated in both the tail and feet of rats. The incidence of necrosis increased with total dose. These total doses, in the range 72-144 Gy, were given as 4-8 treatments of 18 Gy, each dose separated from the next by an interval of 28 days. This treatment protocol minimized acute epithelial skin reactions. The same regime applied to the skin on the back of rats resulted in a very severe acute reaction occurring after the second to fifth dose of 18 Gy. This was surprising since back skin, like tail skin, is less sensitive to large single doses of radiation than that of the foot. The late radiation reaction in the foot and tail of rats are compared and contrasted with other attempts to assess late effects in rodent skin and with late changes seen in pig skin.     

Effects of prolonged low-intensity irradiation on organ weight of the male rat reproductive system

The effects of prolonged irradiation at accumulated doses from 0.5 to 6.0 Gy (dose rate 3.03 cGy/day) on reproductive organs' weight (testes, epididymises, seminal vesicles, prostate) of male rats starting from the early ontogenetic period were studied. On the first day after the irradiation with 1.0 Gy dose a significant loss of the weight in testes and epididymises was revealed. This leaded to the marked atrophy of the organs with the increase of the radiation dose. Long-term restoration of the weight of testes and epididimyses was registered. It was not completed during three months after radiation exposure at 2.0 Gy and higher doses for epididimyses and 4.0-6.0 Gy for testes. The respective changes in the seminal vesicles and prostate weight were less pronounced and had more complicated character. However in the distant period (30-90 days of postreatment) after exposure to 2.0 Gy these parameters were noticeably decreased.     

Radiotherapy: effects on expanded skin

Although the combination of radiation and tissue expansion has been associated with a significant rate of complications, the specific pathophysiology has yet to be clearly elucidated. The objective of this study was to develop a model to identify and examine specific histologic changes associated with tissue expansion and irradiation. Rectangular 50-cc silicone tissue expanders were placed subcutaneously over the midline dorsum of 18 adult New Zealand white rabbits. Preoperative radiographic dosimetry demonstrated that the radiation portal was away from vital intraabdominal structures. The expanders were inflated with 10 cc of saline every other day for a total of 80 cc. Expanders were left in place for 2 to 3 weeks to allow fibrovascular capsule formation. The rabbits were then divided into three groups (six rabbits per group), each receiving one of three nonfractionated doses of radiation (20, 25, or 35 Gy). Half of the expanded skin was irradiated using a single dose, and the other half served as a nonirradiated control. Capsules and skin were harvested 6 weeks after the delivery of radiation, allowing the beginning of chronic radiation changes to occur. Using hematoxylin and eosin staining, histomorphometric analysis was performed. The data were analyzed using Student's test. Although irradiation did not affect dermal thickness, it did cause a statistically significant increase in epidermal thickness. At 20, 25, and 35 Gy the increase in epidermal thickness was 43, 90, and 130 percent, respectively. Although significant epidermal changes could be identified, capsular and dermal alterations were not evident. Further studies evaluating the long-term effects of alterations in capsular formation caused by radiation may be required.     

Dynamics of changes in histomorphometric indices of skin following local irradiation

Recovery of the histomorphometric indices of rat skin at the period from 38 to 150 days following local X-irradiation with doses of 2.5-20 Gy has been studied. It is shown that the rate of restitution of the epidermis and dermis thickness is 0.0021 and 0.0037 days-1, respectively. However, the dermis thickness is less than in the control. The hair follicle density not only fails to restore after irradiation with a dose of above 10 Gy but continues decreasing in time.     

A comparison of the radiation response of the epidermis in two strains of pig

The response of the epidermis was compared in two strains of pig, the English Large White and the G?ttinger Miniature, after irradiation with 90Sr beta rays. The effects of two types of anesthesia were also tested in pigs of each strain, a volatile gas mixture of approximately 70% oxygen, approximately 30% nitrous oxide, and 2% halothane, and an intravenously administered narcotic azaperon/etimodat with the animals breathing air. Strain- and anesthetic-related changes were compared on the basis of dose-effect curves for the incidence of moist desquamation from which ED50 values (+/- SE) were determined, i.e., the dose required to produce this effect in 50% of the fields irradiated. For English Large White pigs anesthetized with the volatile gas mixture, an ED50 of 27.32 +/- 0.52 Gy was obtained for moist desquamation. Irradiation with the azaperon/etomidat anesthesia in this strain of pig produced a significantly higher ED50 of 33.36 +/- 0.76 Gy (P less than 0.001). This appeared to be related to the fact that the animals were breathing air, i.e., a lower oxygen concentration (approximately 21%), at the time of irradiation. For the G?ttinger Miniature pig the ED50 values for moist desquamation were 38.93 +/- 3.12 Gy and 43.36 +/- 1.34 Gy while using the gaseous anesthetic mixture and the azaperon/etomidat anesthesia with the animals breathing air, respectively. These ED50 values are 10-11 Gy higher than those obtained for the English Large White pig under identical conditions of anesthesia, which resulted in a strain difference ratio of approximately 1.35. Radiation under the volatile gas mixture anesthesia resulted in a uniform irradiation response over the skin of the flank in both strains of pig. Radiation under azaperon/etomidat anesthesia resulted in a nonuniform skin response over the flank. The ED50 for moist desquamation was significantly higher in dorsal sites on the flank compared with the ventral area of English Large White pigs; a similar trend was seen in G?ttinger Miniature pigs. This difference in the radiosensitivity over the flank skin while the animals are under azaperon/etomidat anesthesia at the time of irradiation was associated with the animals breathing air and is in agreement with findings published previously for animals under halothane anesthesia and breathing air.     

Incidence of radiation-induced skin tumours in mice and variations with dose rate

Mice were exposed to weakly penetrating beta-particles from an external source, using 12 different surface doses ranging from 5.4 to 260 Gy and given at four different dose rates from 200 to 1.7 cGy/min. As in previous investigations, both epidermal and dermal tumours occurred with the latter predominating. The lowest surface dose to produce a statistically significant increase in skin tumours was 21.7 Gy, no effect being detected with doses of 5.4-16.3 Gy. The dose-response curves rose steeply when obvious increases occurred. Consideration of these findings and the fact that radiation-induced skin tumours can have an exceptionally long latent period leads to the suggestion that there is some relatively radioresistant factor which normally restrains potential radiation-induced cancer cells in the skin from becoming tumours until the skin is subjected to high local doses. Tumour-induction was unaffected by reducing the highest dose rate by a factor of 10 and the dose-response curves were almost identical. Further reductions of dose rate, encompassing a further factor of 10, in general resulted in fewer tumours.     

Effect of irradiation on Mexican leafroller (Lepidoptera: Tortricidae) development and reproduction

The effects of irradiation on egg, larval, and pupal development, and adult reproduction in Mexican leafroller, Amorbia emigratella Busck (Lepidoptera: Tortricidae), were examined. Eggs, neonates, early instars, late instars, early pupae, and late pupae were irradiated at target doses of 60, 90, 120, or 150 Gy, or they were left untreated as controls in replicated factorial experiments. Survival to the adult stage was recorded. Tolerance to radiation increased with increasing age and developmental stage. A radiation dose of 90 Gy applied to neonates and early instars prevented adult emergence. A dose of 150 Gy was not sufficient to prevent adult emergence in late instars or pupae. The effect of irradiation on sterility was examined in late pupae and adult moths. For progeny produced by insects treated as late pupae, a total of three out of 3,130 eggs hatched at 90 Gy, 0 out of 2,900 eggs hatched at 120 Gy, and 0 out of 1,700 eggs hatched at 150 Gy. From regression analysis, the dose predicted to prevent egg hatch from the progeny of irradiated late pupae was 120 Gy, with a 95% confidence interval of 101-149 Gy. The late pupa is the most radiotolerant stage likely to occur with exported commodities; therefore, a minimum absorbed radiation dose of 149 Gy (nominally 150 Gy) has potential as a quarantine treatment. Reciprocal crosses between irradiated and unirradiated moths demonstrated that males were more radiotolerant than females. Irradiation of female moths at a target dose of 90 Gy before pairing and mating with irradiated or unirradiated males resulted in no viable eggs, whereas irradiated males paired with unirradiated females produced viable eggs at 90 and 150 Gy.     

Measured TG-60 dosimetric parameters of the Novoste Beta-Cath 90Sr/Y source trains for intravascular brachytherapy

Measurements were performed on the 30, 40 and 60-mm 90Sr/Y beta-emitter source trains used in the Novoste Beta-Cath system to determine the dosimetric characteristics of the sources at millimeter distances and provide the necessary TG-60 dosimetry parameters for mapping the dose distributions. These measurements were carried out in a Solid Water phantom where MD-55-2 Gafchromic films were placed in direct contact with a 5 French (F) catheter used for the 30 and 60-mm source trains and a 3.5 F catheter used for a thinner 40-mm source train. The dosimetric analysis was performed according to the AAPM TG-60 formalism. For the 30-mm source train, data were collected with the source axis at distances of 0.41 and 1.19 mm from the film surface, respectively, in order to investigate possible dosimetric effects due to the intrinsic off centering of the source train lumen within the 5 F catheter. Absolute dose rates at 2 mm were determined by calibrating the radiochromic film in a high energy electron beam from a radiotherapy accelerator. The dose rates at a radial distance of 2 mm were found to be within 10% of the values provided by Novoste. Radial dose functions from this study were in good agreement (< or = 10%) with a 30-mm, 90Sr/Y source train dose data generated from C. G. Soares et al. 90Sr/Y single seed data. However, larger differences were observed at distances shorter than 1 mm when compared to radial dose functions from the Novoste Monte Carlo data.     

Changes in osteoclasts after irradiation with carbon ion particles

We examined the effects of radiation on decreases in osteoclast numbers after regional irradiation of rats with carbon ions and gamma rays. Male Wistar rats were subjected to hind-leg irradiation with carbon ions (290 MeV/u) or gamma rays at doses of 15, 22.5, or 30 Gy. The effects of carbon ions and gamma rays on osteoclasts were studied using histologic and morphometric methods. At doses of 15 Gy and 22.5 Gy, osteoclast numbers increased transiently until day 5 after irradiation and then decreased rapidly in both the carbon ion and gamma ray irradiation groups. The carbon ion group showed reduced osteoclast size compared with the gamma ray group. Carbon ion irradiation had a more marked effect on osteoclast activity, and suppressed maturation to a greater extent than gamma irradiation. These observations suggest that carbon ion irradiation induces differential modulation of osteoclast growth factor expression.     

The effect of total body gamma-irradiation on mortality, egg production and egg weight of Japanese quails

Male and female Japanese quail 21 weeks old, that were given total body doses of 60Co gamma-rays ranging from 0 to 30 Gy, showed a peak in mortality at 6-8 days post-irradiation. The LD 50/30 was 22.5 Gy, and the LD 90/30 was 26.7 Gy. No differences were evident in mortality between males and females. The reduction in egg production by 30 days post-irradiation was related linearly to the dose, for doses above 6 Gy. The reduction in egg weight (30 days post-irradiation laying period) was also related linearly to the dose.     

Irradiation to ensure quarantine security for Cryptophlebia spp. (Lepidoptera: Tortricidae) in sapindaceous fruits from Hawaii

Studies were undertaken to determine whether irradiation treatment at 250 Gy, an accepted treatment for disinfestation of fruit flies in spindaceous fruits from Hawaii, would also disinfest fruit of two species of Cryptophlebia. Cryptophlebia illepida (Butler) was determined to be more tolerant of irradiation than Cryptophlebia ombrodelta (Lower); therefore, C. illepida was the focus for detailed tests. Using the criterion of success in developing to the adult stage, the pattern of tolerance to irradiation in C. illepida was generally eggs < early instars < late instars < pupae. The most tolerant stage potentially occurring in harvested fruits was late (fourth and fifth) instars. Development to adult was reduced slightly in late instars receiving an irradiation dose of 62.5 Gy, whereas development to adult was dramatically reduced in late instars receiving irradiation doses > or = 125 Gy. No C. illepida larvae receiving an irradiation dose > or = 125 Gy emerged as adults and produced viable eggs, indicating sterility can be achieved at doses well below 250 Gy. In large scale tests, when 11,256 late instars were irradiated with a target dose of 250 Gy, 951 pupated (8.4%) and none eclosed as adults. Within the pupal stage, tolerance increased with age; 7- to 8-d-old pupae (the oldest pupae tested) treated with an irradiation dose of 125 Gy produced viable offspring, whereas those treated with a dose of 250 Gy produced no viable offspring. Irradiation of adults with a target dose of 250 Gy before pairing and mating resulted in no viable eggs. Irradiation of actively ovipositing adult females resulted in no subsequent viable eggs. Therefore, the irradiation quarantine treatment of a minimum absorbed dose of 250 Gy approved for Hawaii's fruits will effectively disinfest fruits of any Cryptophlebia in addition to fruit flies.     

Dose-response curves and tolerance doses for late functional changes in the normal rat brain after stereotactic radiosurgery evaluated by magnetic resonance imaging: influence of end points and follow-up time

Late reaction of normal tissue is still a limiting factor in radiotherapy and radiosurgery of patients with brain tumors. Few quantitative data in terms of dose-response curves are available. In the present study, 99 animals were irradiated stereotactically at the right frontal lobe using a linear accelerator and single doses between 26 and 50 Gy. The diameter of the spherical dose distribution was 4.7 mm (80% isodose). Dose-response curves for late changes in the normal brain at 20 months were measured using T1- and T2-weighted magnetic resonance imaging (MRI). The dependence of the dose-response curves on the follow-up time and the definition of the biological end point were determined. Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were found to be dependent on dose and progressive in time. At 20 months, the tolerance doses at a 50% effect probability level were 39.6 +/- 1.0 Gy and 42.4 +/- 1.4 Gy for changes in T1- and T2-weighted images, respectively. These dose-response curves can be used for further quantitative investigations on the influence of various treatment parameters, such as the application of charged particles, radiopharmaceuticals or the variation of tissue oxygenation.     

Compensatory adjustment of hemopoietic stem cell pool of CBA mice after acute intake of 90Sr

It was investigated the functional status of stem cell pool (CFUs) of bone marrow, spleen and peripheral blood in mice (CBA) in early (1-30 days) and late (180-360 days) period after acute intake of 90Sr (29.6 kBq/g). Cumulative dose in red bone marrow due to incorporated 90Sr was 0.98-87.7 Gy. The kinetics, proliferative and differentiative potential of stem hemopoietic cells (CFUs) and productivity of hemopoietic tissues were significantly influenced by dose rate, absorbed dose and degree of suppresssion of bone marrow functions.The obtained results indicated that the sarcomogenous doses of 90Sr (29.6 kBq/g) resulted in realization of compensatory reactions in hemopoietic stem cell pool to support the life ability of irradiated animals: higher proliferative potential of CFUs and its repopulation, redistribution of cell subpopulations during differentiation and activation of spleens hemopoiesis.     

Acute biological effects of simulating the whole-body radiation dose distribution from a solar particle event using a porcine model

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses.     

Changes in the DNA labelling index after beta irradiation of the mouse epidermis

This study looked at the changes in the interfollicular DNA labelling index (LI) with time after strontium-90/yttrium-90 beta irradiation of approximately 100 mm2 of mouse flank skin, after a dose of 100 Gy which produces transitory moist desquamation. Within 24 hr of such a dose the LI of the irradiated area was essentially zero (0.07 +/- 0.03%), whilst those of the side area and of the control area were 15.0 +/- 2.6% and 21.4 +/- 2.7%, respectively. The LI of the side and the control areas then fell within 3-5 days to approximately 4% and approximately 2% respectively, whilst that of the irradiated area rose rapidly to a peak value of 30.2 +/- 1.7% at 10 days post-irradiation. There was a 20% reduction in the diameter of the area with detectable radiation damage within 5 days, and this is primarily due to cell proliferation and migration from the unirradiated margins of the field. In contrast, between days 10 and 20 the major source of repopulation is probably derived from local migration and proliferation of surviving hair follicle basal cells within the irradiated field.     

Imbalance between apoptosis and proliferation causes late radiation damage of salivary gland in mouse

Severe xerostomia is a common late radiation consequence, which occurs after irradiation of head and neck malignancies. The aim of the present study was to analyze apoptosis and proliferation and their relationship during the late post-irradiation phase. C57BL/6 mice were locally irradiated in head and neck region with a single dose of 7.5 or 15 Gy and their submandibular glands were collected at 40 and 90 days after irradiation. To identify apoptotic cells, the TUNEL method was employed and immunohistochemistry with proliferating cell nuclear antigen (PCNA) was used for detecting proliferation. Histological changes at day 40 were mild in contrast to day 90 when glands of irradiated mice showed severe atrophy, vacuolization and mononuclear infiltration. Acinar cells, granular and intercalated duct cells of mice irradiated with 7.5 and 15 Gy expressed higher apoptotic index than cells of non-irradiated, control glands at both examined time points. At 40 days, a higher proliferation index in granular and intercalated duct cells was detected only in group irradiated with 7.5 Gy. At 90 days, proliferation index for all cell types in both irradiated groups was similar to the controls. According to our results, the imbalance between apoptosis and proliferation caused by X-irradiation may be the reason for gland impairment during the late post-irradiation phase.     

Late effects in the mouse small intestine after a clinically relevant multifractionated radiation treatment

Late radiation effects were investigated in the mouse small intestine after a daily fractionated radiation treatment. Mice were given 14 X 3 Gy in 2 weeks over a partial abdominal irradiation field. There was evidence for late injury in the intestinal epithelium, the submucosa, and the subserosa. Late damage in the epithelium was shown histologically by a reduced crypt number and villus atrophy at 3 and 6 months but not at 24 h after the end of treatment. The reduction in crypt number was significant in the ileum at 3 and 6 months after irradiation: 100 +/- 4 and 98 +/- 5 (SEM) per circumference, respectively, versus 132 +/- 3 and 146 +/- 6 in age-matched controls (P less than 0.01, t test). The mitotic activity in the crypts of the irradiated animals was significantly increased at all investigated times, suggesting a prolonged but insufficient compensatory response to maintain the mucosal integrity. The repercussion on intestinal epithelial function was, at least in part, reflected by a progressively reduced body weight gain up to 5 g at 3 months after treatment. The ability of the surviving crypt stem cells to form microcolonies after irradiation, however, was not impaired. Evidence for injury in the submucosa was provided from macroscopic and histological examination. Macroscopically, at 6 months after treatment, narrowed and rigid bowel segments surrounded by fibrotic adhesions were observed, causing partial intestinal obstruction. In addition, sometimes focal areas of hemorrhage and infarction in small bowel segments were present. Histologically, diffuse and pronounced submucosal edema without increased fibrosis was seen, together with markedly dilated small blood vessels in focal areas of macroscopic intestinal infarction. The intestinal perfusion, as assessed by 86Rb extraction, was significantly but transiently reduced at 3 months after irradiation. These data suggest mainly late effects in the small intestine after this daily fractionated irradiation treatment. The reduced number of epithelial cells and the submucosal edema are possibly mediated by radiation injury in the intestinal microvasculature.     

Fecundity and longevity of Argentine ant (Hymenoptera: Formicidae) queens in response to irradiation

Irradiation is a post‐harvest quarantine treatment option to control ants and other hitchhiker pests on fresh horticultural products traded between countries. As little is known about irradiation effects on ants, radiotolerance of the Argentine ant, Linepithema humile (Mayr) (Hymenoptera: Formicidae: Dolichoderinae), was studied to determine a dose sufficient for its control. Queens collected from Buenos Aires, Argentina, were irradiated with 30, 60, 90 Gy or left untreated as controls, and then followed for 8 weeks to evaluate their survival and fecundity. Overall queen survival and brood viability decreased with increasing irradiation dose. The number of eggs was reduced by 50%, 69% and 56% in the 30, 60 and 90 Gy doses, respectively, compared with untreated control queens. The percentage of eggs that developed into larvae decreased from 41.1% in the control to 22.5%, 1.4%, and 0% in the 30, 60, and 90 Gy treatments, respectively. Thus, the number of larvae was reduced by 69% in the 30 Gy treatment compared with the control, only one larva was observed in the 60 Gy treatment, and none in the 90 Gy treatment. Only one pupa was observed in the 30 Gy treatment and none in the 60 and 90 Gy treatments during the 8‐week experiment. Queens irradiated with 60 and 90 Gy had significantly reduced longevity compared with queens treated with lower doses or untreated queens. Radiation dose ≥90 Gy stopped brood development in Argentine ant queens and should be sufficient as a phytosanitary treatment. The radiotolerance of Argentine ant appears to be similar to that of two other important invasive ants.