Body X-irradiation Research Articles

Statistical modeling of ultrastructural features of murine dermal collagen under chronic low-dose whole body X-irradiation

The present study investigated the changes in ultrastructural features of dermal collagen fibrils of mice following exposure to different cumulative chronic low-dose X-irradiation through digital image analysis-based statistical modeling. Pubertal mice were X-irradiated and dorsal skin biopsies were collected and processed for transmission electron microscopic (TEM) analysis. TEM features of collagen fibrils showed alteration in the cross-sectional area, population density and in the axial periodic pattern of light and dark bands. The mathematical analysis of histogram data from TEM images revealed some adaptive behavior in collagen structures of the X-irradiated group. This finding indicated that exposure to chronic low-dose X-radiation induced an altered steady state with adaptive variation in dermal collagen fibrils in irradiated mice.

Extremely Low Doses of X-Radiation can Induce Adaptive Responses in Mouse Prostate

The pKZ1 mouse chromosomal inversion assay is the only assay that has detected modulation of a mutagenic endpoint after single whole body X-irradiation with doses lower than 1 mGy. A non-linear dose response for chromosomal inversion has been observed in spleen and prostate between 0.001 mGy and 10 mGy, with doses between 0.005-0.01 mGy causing an increase in inversions and doses between 1-10 mGy causing a reduction below spontaneous inversion frequency. An adaptive response is a decreased biological effect induced by a low radiation dose. Adaptive responses contradict the linear-no-threshold model of risk estimation. We demonstrated that very low (0.001 mGy, 0.01 mGy, 1 mGy and 10 mGy) doses of X-radiation induced a chromosomal inversion adaptive response as measured by a reduction in the frequency of subsequent high dose (1000 mGy) induced inversions in prostate. These are the lowest X-radiation doses reported to induce an adaptive response for any endpoint. Adaptive response experiments were also performed where the high dose was administered four hours prior to a low dose of 0.01 mGy or 10 mGy In both cases an adaptive response was observed. Identification of the modifying factors involved in the adaptive response may provide candidates for radioprotection.

Assessment of DNA damage in multiple organs of mice after whole body X-irradiation using the comet assay

The comet assay was performed to elucidate the linearity of calibration curves and detection limits for DNA damage in multiple organs of whole body X-irradiated mice, and rates of reduction in DNA damage by DNA repair during the irradiation period were estimated in the respective organs by comparing the rates of increase in DNA damage at different absorbed dose rates of X-rays. Of the assay parameters, tail length and the percentage DNA in the tail showed a higher sensitivity to DNA damage in most organs than Olive tail moment. Data at the higher absorbed dose rates (2.22 or 1.44 Gy/min) showed good correlations between absorbed doses and these two parameters, with correlation coefficients of more than 0.7 in many organs. However, this assay had difficulty detecting DNA damage at the lower absorption dose rate (0.72 Gy/min). The estimated rates of increase in DNA damage and those of DNA repair during the irradiation period in the respective organs suggested differences in the radiosensitivity of nuclear DNA and DNA repair capacity among organs. Our results indicated that absorbed dose rates of 1.0–1.3 Gy/min or greater were needed to induce detectable DNA damages by the comet assay in many organs.

Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice: Protective effect of α-lipoic acid

Reactive oxygen species are implicated in neurodegeneration and cognitive disorders due to higher vulnerability of neuronal tissues. The cerebellum is recently reported to be involved in cognitive function. Therefore, present study aimed at investigating the role α-lipoic acid against radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body X-irradiation (6 Gy) of mice substantially impaired the reference memory and motor activities of mice. However, acute intraperitoneal treatment of mice with α-lipoic acid prior to irradiation significantly attenuated such cognitive dysfunction. α-Lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of protein carbonyls and thiobarbituric acid reactive substance (TBARS) in mice cerebellum. Further, radiation-induced deficit of total, nonprotein and protein-bound sulfhydryl (T-SH, NP-SH, PB-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by α-lipoic acid pre-treatment. Moreover, α-lipoic acid treated mice showed an intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells in comparison to untreated irradiated mice. Results clearly indicate that α-lipoic acid is potent neuroprotective antioxidant.

Radiation effects to acupuncture in mice embryos

We examined the radioprotection effects of acupoint (acupuncture point) stimulation during organogenesis stages of ICR mice. Pregnant mice received 1.5 Gy whole body X-irradiation on day 8 of gestation, which is the early stage of organogenesis. The embryonic death rate and teratogenesis rate by radiation were examined. Electroacupuncture to the leg acupoints and/ or transcutaneous stimulation to the back acupoints on the pregnant mice showed no protective effect against irradiation on embryonic or fetal death rate. On the contrary, the strong stimulation resulted in increase in the mortality after irradiation rather than protection. However acupoint stimulation to the pregnant mice never showed harmful effects by itself on embryos. It tended to reduce the skeletal malformations induced by X-ray irradiation. We suspect that acupoint stimulation removed the cells injured by irradiation during embryonic development, resulting in an increase in embryonic death rate and reduction in skeletal anomalies.

Acute-phase protein gene expression in rat liver following whole body X-irradiation or partial hepatectomy

We studied the effect of total body X-irradiation and partial hepatectomy on the acute phase protein gene expression in rat liver. Male rats of AO strain were irradiated with high X-ray doses, without any visible tissue damage. In contrast, partial hepatectomy consisted of surgical removal of 40% liver tissue. The changes in liver mRNA concentrations for positive acute-phase reactants including cysteine protease inhibitor, α 1-acid glycoprotein, fibrinogen and haptoglobin, and albumin as a negative reactant were monitored by Northern blot and slot-blot hybridizations using corresponding [ 32P]dCTP labeled cDNA probes. While in the first 24 h after the partial hepatectomy, liver mRNA levels for the positive acute-phase reactants increased, briefly followed by an immediate decrease, the duration and timing of the acute-phase responses to the whole body X-irradiation were slightly different and lasted for as long as 72 h. Although both treatments induced the mRNA expression of acute-phase reactants in rat liver, the observed variations in the duration and intensity of the changes in mRNA levels for the acute-phase proteins in these two types of tissue damage suggest the involvement of specific mechanisms in a fine tuning of the non-specific acute-phase responses to meet the unique requirements of the particular injury.

Cyclosporin A-Induced Autoimmunity in the Rat: Central versus Peripheral Tolerance

No abstract available

The effects of prenatal X-irradiation on hypoglossal nucleus: a GFAP immunohistochemical study.

The effects of prenatal X-irradiation on hypoglossal (XII) nucleus were investigated in the rat. Pregnant animals were exposed to a single whole body X-irradiation on day 11 and 16 of gestation at a does of 1.3 Gy. The offspring were killed at 7-14 days of age for the histological and immunohistochemical observations. Nissl staining revealed no significant changes of XII motoneurons in these experimental animals. In the control case it was of interest that expression of glial fibrillary acidic protein-immunoreactivity (GFAP-IR) is largely confined to the dorsomedial region including the XII nucleus at the level caudal to the obex. Exposure of X-irradiation on day 16 of gestation led to similar expression of GFAP-IR in the nucleus at the same level. However, exposure on day 11 of gestation apparently led to strong expression of GFAP-IR in the XII nucleus at the level caudal to the obex and the expression was observed to extend rostrally. The GFAP-IR cells showed hypertrophy of cell bodies and longer cytoplasmic processes. Horse-radish peroxidase (HRP) injection into the tip of the tongue including the intrinsic muscles resulted in retrograde labeling in the ventromedial portion of the XII nucleus bilaterally from +0.30 to -1.25 mm. The present study would indicate that motoneurons of the XII nucleus supplying mainly the intrinsic and partly the extrinsic tongue muscles are more sensitive to X-ray exposure before the formation of the XII nucleus.

The human bone marrow as an immunoregulatory organ.

It was 45 years ago that in a virtual revolution in thinking in immunology there developed the acceptance and the subsequent expansion of two new dogmas: (1) that to eliminate toxins and pathogens as the major mode of defense, individual immune cells were, in their ontogeny of differentiation, internally programmed to react singly and then clonally against the virtually limitless individual stimuli of the outside world (1–3); (2) that before this programming was manifested the immune system would fail to recognize any antigenic stimulus as foreign, thereby not differentiating non-self from self-recognition. This allowed for non-self-antigens, if introduced in this early stage, to be immunologically tolerated on subsequent testing. In the chronology of the evolution of these two dogmas, there were the earlier descriptions of specific immunological paralysis and unresponsiveness to certain defined polysaccharides and haptens demonstrated in adult mice and guinea pigs respectively by Felton (4) and Chase (5). It remained for Medawar and his colleagues (6) in allotransplantation experiments to clearly define “acquired specific immunological tolerance” as an ontogenic concept involving the lack of maturation or differentiation were tolerance to be evoked. As early as 1953, Billingham, Brent, and Medawar demonstrated that allogeneic donor bone marrow-derived cells could confer such a specifically acquired tolerant state to the immune system of the murine recipient before self versus non-self recognition occurred in immune ontogeny, the test being subsequent acceptance of skin allografts from the same donors. The developmental processes of positive versus negative selection only a decade later began to be demonstrated to predominantly involve the thymus gland in maturational events of cells of the recipient immune system in studies first performed in neonatal rodents (7). By experimental manipulation of the immune system predominantly involving immunoablation by whole body x-irradiation, these findings of specific immunological tolerance as a result of the infusion of bone marrow-derived cells could be extended to adult animals as the system regenerated from stem cells in the bone marrow of either that of the donor (8), the recipient (9), or both (10). Nonetheless, except in the setting of clinical bone marrow transplantation using major (lethal) immunoablation followed by the salvage and replacement of the recipient immunohematopoietic system with donor cell lineages and only in the context of little or no donor-recipient MHC disparity, with few exceptions (11–15), to date, specific immunological tolerance in organ transplantation in humans has not been possible.

Difference in the effects of radioprotection between aerial and root parts of Lycium chinense

Radiation protection from bone marrow death by consecutive injections of crude extracts from different parts of Lycium chinense (LC), root (LCR) and aerial part (LCA), before whole body X-irradiation was confirmed by tests with ICR strain mice. Both extracts were effective after intraperitoneal injection of a high dose, once a day, for seven consecutive days before irradiation. Based on the studies of endogenous hematopoietic spleen colony formation (CFUs), and the postirradiation behavior of hematograms and hematocrits, it was demonstrated that the LCR protects mice more effective when given in a dose of 500 mg/kg. Enhanced CFUs was found in the irradiation range of 4–8 Gy by various treatments. Recovery of leukocyte, erythrocyte and thrombocyte counts was significantly stimulated by the extract of LCR with 500 mg/kg administration. Stimulated recovery by the extract from the LCR was also observed in hematocrit. On the contrary, the extracts of both LCA and LCR did not markedly affect recovery of leukocyte, erythrocyte, thrombocyte counts and hematocrits by 250 mg/kg administration. It could be deduced that the uncertainly radioprotective action is induced by a possible process of enhanced regeneration of the hematopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hematopoietic stem cells under the suitable extract administration.

Radiation-induced apoptosis and gene expression in neonatal kidney and testis with and without protein synthesis inhibition

Purpose: To analyse the incidence of radiation-induced apoptosis, expression of two apoptosis-related genes,Bcl-2 and p53, and post-radiation levels of cell proliferation in the neonatal rat (4-5 days old) kidney and testis. Materials and methods : Apoptosis was quantified in control or treated kidney or testis at 2, 4, 6, 8 and 24h after 5Gy of whole body X-irradiation (n=4 per group). Morphology (light and electron microscopy) and DNA gel electrophoresis were used to assess apoptosis. Temporal and spatial expression of Bcl-2 or p53 were analysed using immunohistochemistry. Administration of cycloheximide (1.5mg/kg) was used to determine whether new protein synthesis had a role in induction of apoptosis. Tritiated thymidine uptake and autoradiography were used to indicate alterations in cell proliferation (radiolabel administered 1h prior to tissue collection) or S-phase cells undergoing radiation-induced apoptosis (radiolabel administered 1h prior to irradiation). Results: Apoptosis peaked at 4h in the testis and 6h in the kidney and was significantly higher in the renal nephrogenic zone than in the testis (p Alt; 0.05). Mitosis was almost completely negated after irradiation in both tissues. A higher proportion (almost fivefold) of the apoptotic cells died in S phase in the kidney than in the testis. Cycloheximide negated induction of apoptosis in the kidney, and markedly decreased apoptosis in the testis. Bcl-2 expression was highest in the differentiated zone of control kidneys and increased after irradiation in the nephrogenic zone, particularly near foci of apoptosis in developing nephrons. In the control testis, Sertoli cells had moderate expression of Bcl-2. After irradiation, there was complete absence of Bcl-2 expression in apoptotic Sertoli cells, with surviving cells increasing Bcl-2 expression. Irradiated kidney had more intense nuclear p53 expression compared with controls. In the testis, p53 that was present in controls continued to be expressed in surviving cells but not apoptotic cells in radiation-treated animals. Conclusions: Unique differences can be identified between the incidence and biomolecular control of radiation-induced apoptosis in the normal neonatal kidney and testis. These results may find application for minimizing damage to these normal neonatal tissues in the development of, for example, cancer treatment regimens.

X-ray-induced lymphomagenesis in E mu-pim-1 transgenic mice: an investigation of the co-operating molecular events.

Transgenic mice overexpressing the pim-1 oncogene in their lymphoid compartment display a low incidence of spontaneous T-cell lymphomas, but are highly susceptible to point mutation-inducing genotoxic carcinogens. We show here that total body X-irradiation, which causes mainly chromosomal deletions, rearrangements and amplifications, significantly enhances lymphoma development in E mu-pim-1 transgenic mice. The X-ray-induced E mu-pim-1 and non-transgenic lymphomas have a comparable high cell turnover as shown by a relatively high S-phase fraction and a high apoptotic activity. Consistent with previous observations, in 75% of all lymphomas c-myc mRNA levels are 5- to 20-fold higher than in control, non-lymphomatous spleen/thymus. The expression of other oncogenes, which have previously found to be activated in combination with pim-1 in lymphomagenesis, such as gfi-1/pal-1, frat-1 and tiam-1, and also of the mdm-2 and mdm-x oncogenes, appeared not to be affected. Deletions and/or rearrangements of the p16INK4A and p15INK4B tumor suppressor genes were seldom observed (in three out of 92 X-ray-induced lymphomas). Strikingly, in addition to the high mRNA levels of the pim-1 transgene, the levels of the endogenous pim-1 transcripts were elevated significantly in 16% of the X-ray-induced E mu-pim-1 lymphomas compared with control spleen, even surpassing the level of the pim-1 transgene mRNA by 3- to 5-fold. In combination with previous results, which showed that the lymphoma incidence increased concordantly with higher levels of pim-1, this supports the notion that pim-1 can contribute to lymphomagenesis in a dose-dependent manner.

Difference in sensitivity of inner cell mass and trophectoderm to X-irradiation in mouse blastocysts.

Pregnant B6C3F1 mice were exposed to a single whole body X-irradiation on day 4 (73-74 hr postconception) of gestation. In experiment 1, they were sacrificed at 2, 4, 6, or 9 hr after a dose of 2 Gy, and their embryos were removed and examined with light and electron microscopy. In experiment 2, dose-response effects of irradiation on the embryos were examined 4 hr after doses of 0-4 Gy. In experiment 3, DNA fragmentation (a marker of apoptosis) was observed by 3'-OH nick-end labeling technique. In inner cell mass (ICM) and trophectoderm (TE) of blastocysts exposed to 2 Gy, cells with cytoplasmic degeneration, or dead cells phagocytosed by their neighboring cells, were found. Although morphological features of these dying cells did not reveal typical characteristics of apoptosis such as nuclear condensation and membrane blebbing, DNA fragmentation was detected by nick-end labeling technique. The degenerated cytoplasm consisted of aggregating ribosomes. Degenerated cells began to increase from 2 hr after irradiation and reached maximal at 4 hr in both ICM and TE. The incidences of degenerated cells in ICM were higher than those in TE at any time point. These findings provide evidence that cell death observed in blastocysts after X-irradiation is apoptotic and sensitivity of the two groups of cells (ICM and TE) to X-rays is different.

Comparative study on the immunocompetent activity of three different kinds of Peh-Hue-Juwa-Chi-Cao,Hedyotis diffusa,H. corymbosaandMollugo pentaphyllaafter sublethal whole body x-irradiation

This brief communication describes the immunocompetent activity of the Chinese folk-medicinal herbs, Hedyotis corymbosa, H. diffusa and Mollugo pentaphylla in mice after moderate whole body x-irradiation. These antitumour drugs, given at doses of 500 and 1000 mg/kg/day for 7 consecutive days before x-irradiation protected ICR strain mice from the sublethal effects of radiation at a dose of 4 Gy, especialy for the dose at 1000 mg/kg. Prior administration of H. corymbosa and H. diffusa ameliorated the leukopenia and splenic cellular decrease induced by sublethal irradiation, and slightly increased the immunocompetence of splenic cells after being stimulated by mitogens. However, administration of M. pentaphylla before x-irradiation exerted a less protective effect on ameliorating leukopenia and on splenic cellular immunocompetence. These findings suggest that some types of Peh-Hue-Juwa-Chi-Caoi (PHJCC) may also be effective in the prevention of haematopoietic damage when used in combination with radiotherapy.

Malignant neoplasms in cyclosporin A-induced autoimmunity (CyA-AI).

Lethally X-irradiated LEW rats reconstituted with syngeneic bone marrow and given low-dose Cyclosporine A (CyA) for 5 weeks develop, after withdrawal of CyA, symptoms of disease resembling graft-vs.-host disease (GVHD) as seen after allogeneic bone-marrow transplantation. Symptoms of disease may include acute dermatitis and chronic disease resembling scleroderma. Since anti-class II MHC cytotoxic lymphocytes are generated in this model, it has been proposed as an anti-tumor regimen in humans. We now report that LEW rats treated according to this protocol may, after cessation of CyA administration, paradoxically develop malignant neoplasms. Of 48 experimental animals, 31 developed rapidly progressive subcutaneous and/or intracutaneous tumors commencing at 6 weeks, 13 weeks and 6 months after cessation of CyA. Tumors were of mesenchymal origin, usually high-grade sarcoma, adenocarcinoma or both mesenchymal and epithelial tumors. Such tumor incidence exceeded the incidence of tumor growth in X-irradiated controls, and in rats subjected to thymectomy prior to X-irradiation and CyA administration. CyA by itself induced no tumors. Our results show that total body X-irradiation is required for tumor development but that the presence of CyA-induced autoimmune disease increases the incidence significantly.

Effective treatment of experimental cytomegalovirus-induced encephalo-meningitis in immunocompromised rats with HPMPC

Cytomegalovirus (CMV)-induced encephalomeningitis is a dramatic complication in patients with the acquired immunodeficiency syndrome (AIDS) and treatment of this infection remains a major clinical problem. In order to study the pathogenesis and treatment of CMV-induced encephalomeningitis, we experimentally induced intracranial rat CMV (RCMV) infection in rats that were immunosuppressed by total body X-irradiation. CMV infection was monitored by viral plaque assay for estimation of the viral load. CMV-induced pathology, the presence of CMV-infected cells, as well as the presence of T-lymphocytes and monocytes/macrophages were studied by histopathologic and immunohistochemical staining techniques. The meninges showed CMV infection in mononuclear infiltrative cells and in endothelium of small blood vessels 8 days after intracerebral inoculation. This was accompagnied by multiple haemorraghes and inflammatory cell infiltration. The infection and inflammatory response persisted for at least 21 days p.i. Animals were treated with ( S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), hyperimmune serum (HIS) and both DHPG and HIS combined. Treatment with one dosage of HPMPC at 20 mg/kg effectively reduced virus titers. However, all other treatment modalities were not effective. In conclusion, the pathology of RCMV-induced encephalomeningitis in immunocompromised rats closely resembles that of AIDS patients. The infection is effectively treated by HPMPC.

Limiting dilution analysis of T-cell progenitors in the bone marrow of thymic lymphoma-susceptible B10 and-resistant C3H mice after fractionated whole-body X-irradiation

. Earlier studies from this laboratory using Thy 1 congenic B10 strain mice suggested that a depletion of T cell progenitors (pre T cells) in the bone marrow in addition to the destruction of the thymus after fractionated whole body X-irradiation (IR) are the two main critical factors that cause differentiation arrest of initially repopulating intrathymic radioresistant T cell progenitors, which then lead to the appearance of preneoplastic, prelymphoma cells, and eventually to highly neoplastic thymic lymphomas under the influence of the thymic environment. In order to explore the significance of the depletion (or reduction) of T cell progenitors in the bone marrow during pathogenesis of radiation-induced thymic lymphomas, we compared the pool size of pre T cells in the bone marrow and the spleens as well as the profiles of the regenerating thymocyte populations between thymic lymphoma induction-susceptible B10 and-resistant C3H strain mice following irradiation. The results indicated that irradiation severely depleted the pre T cells in the bone marrow and the spleens of both lymphoma inductionsusceptible and-resistant mice. They also showed that in C3H mice the differentiation and maturation of intrathymic T cell progenitors which initially repopulated the depleted thymus seemed to proceed normally in spite of the poor cellularity, while this process was greatly suppressed in B10 mice. These data indicate that a depletion of pre T cells in the bone marrow combined with atrophy of the thymus in the irradiated mice is necessary, but not sufficient for development of thymic lymphoma. Implication of these findings on the possible mechanism of radiation-induced thymic lymphomagenesis is discussed.

In Situ Radiation Sensitivity of Recombinant Human Granulocyte Colony-Stimulating Factor–Recruited Murine Circulating Blood and Bone Marrow Progenitors (Colony-Forming Unit [CFU]–Granulocyte-Macrophage and CFU-Megakaryocyte): Evidence for Possible Biologic Differences Between Mobilized Blood and Bone Marrow

Increasing evidence especially stemming from peripheral blood progenitor transplantation studies points to a possible biologic difference between mobilized blood and bone marrow progenitor cells. The objective of this study was to compare the in situ radiation sensitivity of recombinant human granulocyte colony-stimulating factor (rhG-CSF)-recruited circulating granulopoietic (blood colony-forming unit-granulocyte-macrophage [CFU-GM(blood)]) and megakaryocytopoietic (blood CFU-megakaryocyte [CFU-Meg(blood)]) progenitors, with the nonmobilized fraction remaining in the bone marrow (CFU-GM(femur) and CFU-Meg(femur)). Splenectomized male B6D2F1 mice received 50 micrograms/kg/d rhG-CSF daily for 8 days to induce high levels of circulating progenitors, followed by either total body X-irradiation (TBI) or X-irradiation of the chest (CI) with 62.5, 125, 250, or 500 cGy. Progenitor cells were assayed 24 hours after irradiation. Circulating CFU-GM and CFU-Meg in the blood were decreased in a dose-dependent fashion by both TBI and CI, with TBI causing greater damage than CI. Average D0 values for TBI were 53 cGy for CFU-GM(blood) and 40 cGy for CFU-Meg(blood) D0 values for CI were 90 cGy for CFU-GM(blood) and 140 cGy for CFU-Meg(blood). As seen for blood progenitor cells, TBI caused a dose-dependent decrease of both CFU-GM(femur) (D0, 136 cGy) and CFU-Meg(femur) (D0, 148 cGy). However, radiation-induced bone marrow progenitor cell kill was significantly lower when compared with blood progenitors. Despite the fact that circulating blood elements only received a fraction of the total dose administered as Cl, the extent of blood progenitor kill caused by Cl was higher than the effects of identical TBI doses on bone marrow CFU. The results of this study showed that rhG-CSF-recruited CFU-Meg(blood) and CFU-GM(blood) were considerably more radiosensitive than femoral progenitors, thereby providing novel evidence for a biologic difference between rhG-CSF-recruited peripheral blood progenitors and the nonrecruited bone marrow CFU.

Role of natural effector cells in the prevention of radiation-induced leukemogenesis

Four once-weekly exposures of 225 rads (R) of whole body X-irradiation causes a high incidence of lymphoma in C57BL/6 (C57) mice. The role of natural effector cells in radiation-induced leukemogenesis was investigated. Activity of natural killer (NK) and natural cytotoxic (NC) cells was depressed in irradiated mice over a prolonged period. Transplantation of bone marrow (BM) cells from normal C57 mice to irradiated mice restored their NK responses and prevented development of lymphoma. The effect of beige BM cell transfer to irradiated mice was not clear. Unlike short-term (4-hour) assay, results of long-term (20-hour) assay suggest partial restoration of NK and full restoration of NC activity in irradiated mice. Treatment of irradiated mice with polyinosinic: polycytidillic acid (poly I:C) increased NK activity and lymphoma resistance. Administration of small repeated doses of poly I:C to irradiated mice significantly prevented the development of lymphoma as well as significantly prolonging overall survival time in irradiated mice. These observations indicate that natural effector cells mediate resistance to radiation-induced leukemogenesis.

A quantitative study of the effects of prenatal X-irradiation on the development of cerebral cortex in rats

Pregnant rats were exposed to a single whole body X-irradiation on day 15 of gestation at a dose of 1.0 Gy. The offspring showed microcephaly at 7 weeks of age. Their body weight, brain weight, cortical thickness and the numerical density of neurons and synapses in the somatosensory and visual cortex were examined. Significant decreases in cortical thickness in both somatosensory (25%) and visual (16%) cortex were observed. However, there were no significant changes in the numerical density of neurons and synapses, nor in synapse-to-neuron ratios in both cortical regions between control and X-irradiated groups. These results suggest that prenatal X-irradiation can decrease the number of neurons, and the neurons which survive X-irradiation proliferate and elaborate connections in a normal fashion. This is in contrast to the animals exposed to ochratoxin A, in which numerical density of neurons in the somatosensory cortex is increased, with normal numerical density of synapses, resulting in low synapse-to-neuron ratios. The discrepancy in the synapse-to-neuron ratios between the X-irradiation and ochratoxin A-treatment might derive from a different effect on the developing neurons.