Effects of single-dose external gamma irradiation on rat thyroid status as observed during the year

We studied the rat thyroid status depending on the dose of external radiation and the time passed after the exposure. The experiments were carried out on female albino Wistar rats. The doses absorbed amounted to 0.25; 0.5; 1.0; 2.0 and 5.0 Gy. The animals were decapitated after 3, 6, 24 hours and 7, 30, 180 and 365 days following the radiation. The blood serum was assayed for the contents of thyroxin (T4) and triiodothyronine (T3) using a radioimmunological technique. The liver tissue was assayed spectrophotometrically for the activity of thyroid-induced NADP malate dehydrogenase (NADP-MDH). No changes were found in the blood thyroid hormone contents within short periods after the radiation effect. After 6 hours the T4 levels was 1.2-1.3-fold decreased in the blood of rats receiving the radiation doses of 1.0; 2.0; and 5.0 Gy. After a day the T4 concentration was diminished by 1.21-193-fold in all the experimental animals independently of the radiation dose and that of T3--in 2.0 Gy--and 5.0 Gy--irradiated group. After 7 days following the radiation the T4 and T3 contents remained to be decreased by 1.37-1.75 fold and those of NADP-MDH--by 1.3-1.8-fold in all the animal groups. In a month, the low dose-treated animals (0.25, 0.5, 1.0 Gy) showed the level of thyroid hormones reduced to the control values, whereas the 2.0 and 5.0 Gy--treated rats demonstrated this reduction only by 6 months. The decreased concentration of blood thyroid hormones was due not to the activation of their peripheral metabolism, but, probably, to inhibition of their biosynthesis in thyroid cells under conditions of radiation-induced activation of oxidative stress.     

Functional and morphological characterization of rat thyroid gland at remote periods following single high and low dose radiation exposure

A study of the morphological structure and functional activity of the rat thyroid gland was carried out after 22 months following a single exposure to external radiation. The 3-month-old animals were irradiated with doses of 0.25, 0.5, 1.0, 2.0 and 5.0 Gy. Blood was assayed for thyroxin (T4) and triiodothyronine (T3) levels, while liver tissue--for NADP-MDH activity and thyroid tissue--for thyroperoxidase activity. The thyroid was studied histologically, morphometrically and by electron microscope. The decreased T4 concentrations 2.59-fold in the 5.0 Gy group, the increased T3/T4 in the 2.0 and 0.25 Gy groups, the reduced diameter of cellular nuclei and follicles, the flat follicular epithelium and diminished number of thyrocyte ultrastructures indicate thyroid hypofunction in the irradiated animals. The morphological changes are characterized by enhanced diffuse and focal sclerotic changes in thyroid, most pronounced at high irradiation doses (1.0-5.0 Gy), whereas the hemosiderosis foci suggest that the structural changes are consequences of radiation-induced destructive injuries in the gland parenchyma. Two of the thyroids (0.5 Gy) demonstrate foci with pronounced lymphoid infiltration, while follicular carcinomas were detected in 4 thyroids (2.0 Gy), and in one thyroid (0.5 Gy) in one thyroid (5.0 Gy). The remote effects of radiation were dose-dependent destructive, sclerotic and atrophic processes, decreased functional activity, stimulation of development of autoimmune aggression and carcinogenesis in thyroid.     

Concentration of T3 and T4 in blood of non-irradiated and irradiated with different doses rats fasted for two days beforehand

There were no changes in concentration of T3 and T4 in blood of the rats that were irradiated with a dose of 0.5, 1, 2, 4 and 6 Gy in comparison with non-irradiated rats, if the animals were not fed for two days before decapitation. This suggests that the effect of ionizing radiation on thyroid function is mediated by anorexia syndrome. The decrease in concentration of T4 after exposure to 8 Gy cannot be explained by postradiative anorexia and most likely is connected with starting enterotoxemy in difficult cases of acute radiation sickness.     

The effect of long-term external ionizing radiation on the functional activity of rat thyroid under enhanced potassium iodide consumption

The study was devoted to the effect of long-term (20 days) external ionizing radiation at a dose of 0.5 Gy on the iodide metabolism in the rat thyroid under supplementation of high iodine doses (10 daily KI doses). It was found that the potassium iodide administration partially prevented the effects of a post radiation decrease of serum thyroid hormone levels (the level of T4 was normal and that of T3 was 77.4% of the controls). After the supplementation of 10 daily iodide doses, the rat thyroid tissue showed the most pronounced increase in the levels of total, free and protein-bound iodide compared to the groups of animals consuming normal and elevated KI doses. Pronounced inhibition of thyroid peroxidase activity (3.1-fold) was noted in the same group. The data obtained indicate a radiation-induced activation of iodide uptake during its enhanced supplementation and disturbed iodide enzymatic oxidation and organification.     

Low-dose total-body γ irradiation modulates immune response to acute proton radiation

Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate γ rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with ??Co (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to γ rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to γ rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+ T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with γ radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate γ rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations.     

Differential expression of oxidative stress and extracellular matrix remodeling genes in low- or high-dose-rate photon-irradiated skin

Changes in the expression of genes implicated in oxidative stress and in extracellular matrix (ECM) remodeling and selected protein expression profiles in mouse skin were examined after exposure to low-dose-rate or high-dose-rate photon irradiation. ICR mice received whole-body γ rays to total doses of 0, 0.25, 0.5 and 1 Gy at dose rates of 50 cGy/h or 50 cGy/min. Skin tissues were harvested for characterization at 4 h after irradiation. For oxidative stress after low-dose-rate exposure, 0.25, 0.5 and 1 Gy significantly altered 27, 23 and 25 genes, respectively, among 84 genes assessed (P < 0.05). At doses as low as 0.25 Gy, many genes responsible for regulating the production of reactive oxygen species (ROS) were significantly altered, with changes >2-fold compared to 0 Gy. For an ECM profile, 18-20 out of 84 genes were significantly up- or downregulated after low-dose-rate exposure. After high-dose-rate irradiation, of 84 genes associated with oxidative stress, 16, 22 and 22 genes were significantly affected after 0.25, 0.5 and 1 Gy, respectively. Compared to low-dose-rate radiation, high-dose-rate exposure resulted in different ECM gene expression profiles. The most striking changes after low-dose-rate or high-dose-rate exposure on ECM profiles were on genes encoding matrix metalloproteinases (MMPs), e.g., Mmp2 and Mmp15 for low dose rate and Mmp9 and Mmp11 for high dose rate. Immunostaining for MMP-2 and MMP-9 proteins showed radiation dose rate-dependent differences. These data revealed that exposure to low total doses with low-dose-rate or high-dose-rate photon radiation induced oxidative stress and ECM-associated alterations in gene expression profiles. The expression of many genes was differentially regulated by different total dose and/or dose-rate regimens.     

Prenatal exposure of the fetal rat to excessive L-thyroxine or 3,5-dimethyl-3'-isopropyl-thyronine produces persistent changes in the thyroid control system

Studies were conducted to determine if brief exposure, in utero, to high levels of T4 or to the synthetic thyromimetic agent 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) can produce permanent disruption of the thyroid control system in a manner analogous to the changes in the "set point" reported to occur due to neonatal T4 exposure in the "neo-T4 syndrome". If such a change were to occur, it could explain the persistent thyroid disturbances seen in the progeny of hypothyroid mother rats. These latter progeny are exposed in utero to both low and high serum T4 levels. Maternal T4 treatment produced a 4-fold elevation in fetal serum T4 accompanied by a large decrease in serum TSH levels. The brief treatment in utero with high doses of T4 or of DIMIT resulted in higher neonatal mortality and the T4-treatment produce subsequent growth stunting. These treatments resulted in suppression of the fetal/neonatal thyroid which was very apparent at 5 days of age. At 30 days post-partum, the thyroid control system of the progeny of the T4 and DIMIT-treated animals was still abnormal with low serum T4 levels accompanied with normal serum TSH and T3 levels. At 60 days of age, serum T4 levels remained low in the progeny of the T4-treated animals and the TSH response to TRH was subnormal in both the progeny of the T4-treated and the DIMIT-treated animals. However, serum and pituitary TSH and serum T3 were normal. The thyroid control system of the rat is sensitive to prenatal exposure to hyperthyroxinemia as it is to postnatal exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reaction of posterity of two generations after exposure of pregnant Wistar rats to low dose irradiation during the period of fetus formation. Development of the first generation posterity

Whole-body single exposure of female Wistar rats to 0.25, 0.5 and 1 Gy of gamma-rays (dose rate of 0.03 cGy/s) on the 10th day of pregnancy (a period of formation of the reproductive system in fetus) was carried out. To study irradiation consequences on the antenatal and postnatal development of the progeny 220 females, 700 19-day-old fetuses and about 1100 young rats were examined. The antenatal development of the progeny of the first generation was significantly impaired after the exposure to 1 Gy. However even less radiation doses resulted in a pronounced tendency to higher rates of intrauterine death and a lower number of live fetuses. Significant deviatins in the postnatal development of the first generation progeny were found after the exposure to 0.5 Gy, although the exposure to 0.25 Gy led to a higher rate of postnatal death and a less number of newborns in the litter.     

The effect of one-time external low- and high-dose gamma-irradiation on rat thyroid structure at the acute and remote periods

A study of the morphological structure of the thyroid was made at the acute (1, 3, 6 hours) and remote periods (1, 4, 24, 48 weeks) following the external gamma-irradiation at doses of 0.25-5.0 Gy using histologic and electron microscopic methods. At the acute period, morphological changes prevailed, which reflect the functional alterations (changes of the nucleic and of the follicular diameters and of the colloid density). Frequently they hare a non-synchronous character. At more remote periods, destructive (colloidorrhage, desquamation, hemorrhage) and reparative changes reveal in thyroid, which and by the development of the sclerotic processes and of the morphological signs of decreased functional activity of the gland (increased follicular size and colloidal density, flatness of follicular epithelium and pronounced decreasing of the thyrocytes ultra structure number). The presence of such morphological changes after high and low-dose irradiation (<1.0 Gy) shows high sensitivity of the thyroid to single external radiation.     

Increase of probability of cell loss in the endothelium of blood vessel capillaries in progeny of rats after a low-dose irradiation of one of the parents (electron microscopy study)

The total gamma-irradiation of Wistar rats at a dose of 0.25 Gy as well as at higher doses (0.5, 2 and 4.5 Gy) produces in the capillary endothelial cells of myocardium and lung a pronounced, dose-independent increase of the yield of necrotized cells. Similar changes were revealed in the animals, of which one of the parents (a male one day, a female seven days prior to copulation) was irradiated at doses of 0.25 and 0.5 Gy. This effect was observed in all studied descendants. The massive induction of the changes already by low radiation actions and their dose-independence allow considering the revealed effects as a manifestation of peculiar cellular reactions that presumably have epigenetic nature.     

Genetic consequences of irradiation of one or both parents (results of experiments on Wistar rats) Exitus lethalis in Wistar rat's progeny after irradiation of one or both parents

Examination of 2563 offsprings of Wistar rats after irradiation of one or both parents with doses of 0.25, 0.5, 1, 2, 3 and 4 Gy was carried out; the manifestation of lethal effects in the progeny of the first generation in ontogenesis was studied. The level of embryonic death was the highest after irradiation of germ cells of parents at stages of spermatids, spermatozoids and matured oocytes. Following irradiation of both parents with doses of 0.25, 0.5 and 1 Gy at these stages of gametogenesis and 4 Gy at the stage of spermatids and matured oocytes there was a trend of increasing radiation effects caused by the participation of two irradiated germ cells. After irradiation of both parents with doses of 2, 3 and 4 Gy the embryonic death F1 was essentially the same as rates for irradiated females and non-irradiated males. The F1 death rate in early postnatal development exceeded the control only after irradiation with doses of 2, 3 and 4 Gy. The increase in radiation effects in the F1 due to the mating of two irradiated parents appears to be associated with a mechanism demonstrating additivity or synergism.     

Radiation-induced increase in expression of the alpha IIb beta 3 integrin in melanoma cells: effects on metastatic potential.

We investigated the effects of nonlethal gamma radiation on the metastatic potential of the murine tumor cell line, B16 melanoma. The ability of B16 cells to adhere to fibronectin, which is in part mediated by the alpha IIb beta 3 integrin receptor, is predictive of metastatic potential. We determined that exposure to 0.25-2.5 Gy gamma radiation significantly enhanced B16 cell adhesion to fibronectin. The radiation-enhanced adhesion was dependent on enhanced expression of the alpha IIb beta 3 integrin. We observed that 15 min after 0.5 Gy radiation, 99% of irradiated B16 tumor cells were positively labeled with monoclonal antibodies directed against alpha IIb beta 3 compared to 22% of sham-irradiated cells. Radiation-enhanced expression of the alpha IIb beta 3 receptor is reversible and down-regulation begins within 2-4 h postirradiation. Finally, we found that irradiation significantly enhanced the ability of B16 cells to form metastases in a lung colony assay. It is concluded that a relationship exists between radiation effects on the B16 tumor cells, alpha IIb beta 3 receptor expression, adhesion in vitro, and metastasis in vivo. We suggest that low-dose radiation, at levels comparable to those used in fractionated or hyperfractionated radiotherapy, may alter the metastatic phenotype and potential of surviving tumor cells via a rapid alteration in their surface expression of alpha IIb beta 3 integrin receptors.     

Effect of thyroid hormones on the activity of hepatic glucose-6-phosphatase in fed and fasted rats

The action of thyroid hormones on hepatic glucose-6-phosphatase was studied in rats. Fed and 24-h fasted rats received T3 (10 micrograms/day) or T4 (25 micrograms/day) 1 h, 1 or 3 days before sacrificing. In addition a group of fed rats was treated with T4 for 7 and 14 days. The glucose-6-phosphatase activity was measured in the isolated microsomes prepared from the liver. The intactness of the microsomal preparation was checked using 2 mM mannose-6-phosphate as a substrate. In fed rats a single injection of T3 or T4 augmented the activities of the translocase and hydrolase components of glucose-6-phosphatase provided that the rats were killed 24 h after the administration of hormone. This effect was more pronounced in animals treated for 3-14 days. As expected, fasting per se increased the activities of both components of the enzyme. Moreover, in fasted rats treatment with T3 and T4 for 3 days further augmented the activities of the translocase and the hydrolase components of glucose-6-phosphatase. In fed animals T3 and T4 increased the latency of the enzyme whereas in fasted animals thyroid hormones increased the activities of the translocase and hydrolase components in parallel, maintaining the level of latency of the enzyme system. Administration of T3 and T4 increased blood glucose level in fasted rats after one day, while in fed rats a significant hyperglycaemia appeared after 7-14 days of treatment. In conclusion, T3 and T4 increase the activities of the translocase and hydrolase components of hepatic glucose-6-phosphatase in fed and fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Total-body irradiation with high-LET particles: acute and chronic effects on the immune system

Although the immune system is highly susceptible to radiation-induced damage, consequences of high linear energy transfer (LET) radiation remain unclear. This study evaluated the effects of 0.1 gray (Gy), 0.5 Gy, and 2.0 Gy iron ion (56Fe(26)) radiation on lymphoid cells and organs of C57BL/6 mice on days 4 and 113 after whole body exposure; a group irradiated with 2.0 Gy silicon ions (28Si) was euthanized on day 113. On day 4 after 56Fe irradiation, dose-dependent decreases were noted in spleen and thymus masses and all major leukocyte populations in blood and spleen. The CD19(+) B lymphocytes were most radiosensitive and NK1.1(+) natural killer (NK) cells were most resistant. CD3(+) T cells were moderately radiosensitive and a greater loss of CD3(+)/CD8(+) T(C) cells than CD3(+)/CD4(+) T(H) cells was noted. Basal DNA synthesis was elevated on day 4, but response to mitogens and secretion of interleukin-2 and tumor necrosis factor-alpha were unaffected. Signs of anemia were noted. By day 113, high B cell numbers and low T(C) cell and monocyte percents were found in the 2.0 Gy 56Fe group; the 2.0 Gy 2)Si mice had low NK cells, decreased basal DNA synthesis, and a somewhat increased response to two mitogens. Collectively, the data show that lymphoid cells and tissues are markedly affected by high linear energy transfer (LET) radiation at relatively low doses, that some aberrations persist long after exposure, and that different consequences may be induced by various densely ionizing particles. Thus simultaneous exposure to multiple radiation sources could lead to a broader spectrum of immune dysfunction than currently anticipated.     

Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent

The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.     

Developmental plasticity in thyroid function primed by maternal hyperleptinemia in early lactation: a time-course study in rats

Pups whose mothers were leptin-treated during the last 3 days of lactation have thyroid dysfunction at adulthood. However, there was no report about leptin treatment in the first days of life or about its action on thyroid function during development. Here, we evaluated the effects of maternal leptin treatment on the first 10 days of lactation upon thyroid function of the offspring at 21, 30, and 180 days old. At birth, lactating Wistar rats were divided into: Leptin (Lep) - leptin-treated (8 μg/100 g of body weight, s.c.) for the first 10 days of lactation and Control (C, saline-treated). Mothers were killed at the end of lactation and their offspring at 21, 30, and 180 days old. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and leptin levels in serum and milk were measured. Liver mitochondrial glycerolphosphate dehydrogenase (mGPD) activity was determined. Significant differences had p<0.05. At the end of lactation, Lep mothers had higher milk T3 (+ 30%), while their offspring had higher serum T3 (+ 20%) and TSH (+ 84%). At 30 days-old, Lep offspring showed lower TSH ( - 48%), T3 ( - 20%), and mGPDm ( - 42%). At 180 days-old, Lep group presented hyperleptinemia (1.4-fold increase), higher serum T3 (+ 22%), and lower mGPD activity ( - 57%). Maternal hyperleptinemia on lactation causes hypothyroidism in the pups at 30 days, which may program for higher serum T3 at adulthood. In conclusion, maternal hyperleptinemia during lactation, that is common in obese mothers, may have an impact in future disease development, such as thyroid dysfunction.     

Histological changes in spleens of radio-sensitive and radio-resistant mice exposed to low-dose X-ray irradiation

We have previously determined by using immune-assay or bio-assay methods that low-dose irradiation enhances immune and anti-oxidation functions. In this study, we examined histological changes of lymphatic follicles at 4, 24, or 48 hrs after sham, 0.25, 0.5, or 15 Gy irradiation in the spleens of BALB/c mice, which are sensitive to radiation compared with other strains, and C57BL/6J mice, which are resistant to radiation, using hematoxylin-eosin staining for lymphatic follicles or methylgreen pyronin staining for plasma cells. Results show that the lymphatic follicles in the spleens of the two mouse strains decreased at 24 or 48 hrs after 15 Gy irradiation. The number of plasma cells in the spleens of sham irradiated BALB/c mice was greater than that of sham irradiated C57BL/6J mice. At 4 hrs after 0.25 Gy irradiation, plasma cells increased in the spleens of the two mouse strains. These findings suggest, by histology, that low-dose irradiation activates the plasma cells and enhances the immune function. Although those two mouse strains have different sensitivities to radiation, the above changes were similar in both time course and degree of response. Therefore, the phenomena observed may be common in mice.     

Effect of the exposure to chronic-intermittent cold on the thyrotropin and thyroid hormones in the rat

Rats exposed to acute cold (4 degrees C for 2 h), chronic cold (4 degrees C), and chronic-intermittent cold (4 degrees C for 2 h daily) were killed after 1, 2, 3, 4, and 10 days of cold exposure. The control group was maintained at 25 degrees C. In each animal, the plasma concentration of thyrotropine (THS), triiodothyronine (T3), and thyroxine (T4) was determined by radioimmunoassay. At the initial time of exposure, elevations in TSH, T3, and T4 were observed in the rats in each experimental group. However, on the 10th day, in rats exposed to chronic-intermittent cold, TSH, T3, and T4 decreased to values lower than the control values. In animals exposed to acute cold as well as to chronic cold no differences were found, with respect to the controls, in TSH and T4. In rats exposed to acute cold for 10 days, the T3 value was lower than the control value; however, in animals exposed to chronic cold, T3 was same as that in the controls. The results indicate that, in the rat, exposure to chronic-intermittent cold produces an inhibition in the secretion of TSH and thyroid hormones.     

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.     

Long-term dose response of trabecular bone in mice to proton radiation

Astronauts on exploratory missions will experience a complex environment, including microgravity and radiation. While the deleterious effects of unloading on bone are well established, fewer studies have focused on the effects of radiation. We previously demonstrated that 2 Gy of ionizing radiation has deleterious effects on trabecular bone in mice 4 months after exposure. The present study investigated the skeletal response after total doses of proton radiation that astronauts may be exposed to during a solar particle event. We exposed mice to 0.5, 1 or 2 Gy of whole-body proton radiation and killed them humanely 117 days later. Tibiae and femora were analyzed using microcomputed tomography, mechanical testing, mineral composition and quantitative histomorphometry. Relative to control mice, mice exposed to 2 Gy had significant differences in trabecular bone volume fraction (-20%), trabecular separation (+11%), and trabecular volumetric bone mineral density (-19%). Exposure to 1 Gy radiation induced a nonsignificant trend in trabecular bone volume fraction (-13%), while exposure to 0.5 Gy resulted in no differences. No response was detected in cortical bone. Further analysis of the 1-Gy mice using synchrotron microCT revealed a significantly lower trabecular bone volume fraction (-13%) than in control mice. Trabecular bone loss 4 months after exposure to 1 Gy highlights the importance of further examination of how space radiation affects bone.