Effect Of Whole-body X-irradiation Research Articles

Influence of Whole Body X-irradiation on the Liver and Possible Protective Effect by the Compatible Solute Ectoine in a Mouse Model

Exposure of mammals to ionizing radiation leads to the development of a complex dose-dependent series of physiological and pathological changes. The present study was undertaken to investigate the effect of whole body x-irradiation of male mice with a single w dose of 6 Gy on the levels of some cytokines and parameters of oxidative stress, after one and seven days, in the liver. The possible protective effect of the compatible solute ectoine, which is known to reduce cell stress effects on the molecular level, was evaluated. The x-irradiated mice showed elevated interleukins in the liver. The levels of both the pro-inflammatory (IL-1β and IL-6) and the anti-inflammatory (IL-10) interleukins reached several times the control value with quantitative differences. The disturbance by low-dose x-irradiation also affected PGE2. Malondialdehyde, used as indication of oxidative stress, was elevated in the livers of x-irradiated mice. Although, there were no statistically significant differences in the results of total glutathione among the irradiated mice as compared to control values, there were differences among the values of the reduced and oxidized forms. The calculated redox potentials, showed some variations in the different groups, but were all within the values indicating that the cells are in the proliferative phase and far from the apoptotic phase. Treatment with ectoine modulated all the tested biochemical effects induced by x-irradiation in the liver. All the tested parameters had a tendency to go back to near control values.

Effect of whole-body x-irradiation on antigen-induced airway response in sensitized guinea pigs.

The objectives of this study were to test the hypothesis that x-irradiation inhibits the late asthmatic response (LAR) without influencing the early asthmatic response (EAR) and to examine the mechanism of the inhibitory effect. Twenty sensitized guinea pigs were irradiated at a dose of 8 Gy. The next day, one-half of the animals were injected intravenously with spleen cells (2 x 10(8)) collected from unirradiated sensitized guinea pigs, whilst the other half were injected with vehicle only. Ten additional unirradiated sensitized guinea pigs also received vehicle only. Antigen inhalation challenge took place two days later. Pulmonary resistance was measured for 6 h after antigen exposure, and bronchoalveolar lavage and lung fixation were then undertaken. The area under the percentage pulmonary resistance curve 2-6 h after allergen inhalation was used for analysis of the LAR, while the maximal percentage change in pulmonary resistance was used for analysis of the EAR. Irradiation abolished the LAR (364.4+/-49.4 versus 62.8+/-10.4) without inhibiting the EAR (229.3+/-27.2 versus 278.7+/-40.2) and significantly inhibited the accumulation of eosinophils and lymphocytes in the airways. Transfer of spleen cells restored the LAR (334.4+/-66.8) and the recruitment of cells to the levels seen in unirradiated sensitized guinea pigs. In addition, transfer of only CD4+ T-lymphocytes separated from the spleen cells restored the LAR (439.4+/-62.1) and the cell infiltration into the airways. These inhibitory effects of x-irradiation were due to decreases in numbers of CD4+ T-lymphocytes.

P53‐dependent X‐ray‐induced modulation of cytokine mRNA levels in vivo

In vitro studies have shown that ionizing radiation can cause increases in some cytokine mRNA levels and activation of the nuclear NF-κB and/or AP1 transcription factors which have been implicated in the transcriptional regulation of many cytokine genes. Thus, radiation-induced upregulation of cytokine mRNAs appeared to be in part a direct consequence of transcription factor activation. To test this in vitro model in vivo, the effects of whole-body X-irradiation (0–10 Gy) on cytokine and other gene mRNA levels have been examined in mice. Increases and decreases in cytokine mRNA levels were detected in tissues which underwent an early wave of apoptosis (bone marrow and/or spleen), but not in more radioresistant tissues (kidney, liver, brain, and heart). Some mouse strain-specific differences were observed, but none of the changes in mRNA level was detected in p53−/− mice. As activation of the NF-κB and AP1 transcription factors was not detected in early-(spleen) or late-(liver) responding tissues in 10 Gy X-irradiated p53+/+ mice in vivo, it is concluded that the modulation of cytokine gene expression in vivo is p53-dependent and indirectly associated with apoptosis. © 1998 John Wiley & Sons, Ltd.

P53-dependent X-ray-induced modulation of cytokine mRNA levels in vivo.

In vitro studies have shown that ionizing radiation can cause increases in some cytokine mRNA levels and activation of the nuclear NF-kappa B and/or AP1 transcription factors which have been implicated in the transcriptional regulation of many cytokine genes. Thus, radiation-induced upregulation of cytokine mRNAs appeared to be in part a direct consequence of transcription factor activation. To test this in vitro model in vivo, the effects of whole-body X-irradiation (0-10 Gy) on cytokine and other gene mRNA levels have been examined in mice. Increases and decreases in cytokine mRNA levels were detected in tissues which underwent an early wave of apoptosis (bone marrow and/or spleen), but not in more radioresistant tissues (kidney, liver, brain, and heart). Some mouse strain-specific differences were observed, but none of the changes in mRNA level was detected in p53-/- mice. As activation of the NF-kappa B and AP1 transcription factors was not detected in early-(spleen) or late-(liver) responding tissues in 10 Gy X-irradiated p53+/+ mice in vivo, it is concluded that the modulation of cytokine gene expression in vivo is p53-dependent and indirectly associated with apoptosis.

Long-term effect of whole-body X-irradiation on cell-mediated immune reaction in mice.

Age-related change in immunological activity was examined at 10 to 91 weeks following whole-body irradiation by determining the specific anti-tumor cell-mediated immunity in host mice induced and/or enhanced by local irradiation to transplanted tumor. Median survival time of the non-irradiated C3H/He female mice was 98.6 weeks while the median life-span of the mice exposed to two and four Gy of 250kVp X-rays at the age of 10-12 weeks was shortened by 14.9 and 23.4 weeks, respectively. The rate of tumor reduction within two weeks after local irradiation to tumor and the growth inhibitory activity of spleen cells from tumor irradiated mice were reduced in a dose-dependent manner when assessed 10 weeks after whole-body irradiation, but recovered to the near-complete level of the non-irradiated controls within a few months, then gradually decreased with normal aging. These results suggest that the age-dependent decline of this immunological activity appears earlier in the irradiated mice as a result of whole-body X-irradiation at a young age, suggesting accelerated aging of the immune system.

Cell kinetic studies of the effect of a combined therapy with 1-beta D-arabinofuranosylcytosine (Ara-C) and X-irradiation on the L1210 ascites tumour.

We studied the effect of combined therapy with X-ray and 1-beta-D-arabinofuranosylcytosine (Ara-C); firstly the effect of whole-body X-irradiation alone on the proliferation of the L1210 ascites tumour of the mouse was studied by autoradiographic and cytofluorometric (FCM) methods. The effect X-irradiation with 4 Gy was mainly a cytostatic one leading to an altered distribution of the cells throughout the cycle due to radiation induced mitotic delay. The cytocidal effect is negligible. As is known from previous studies (Fietkau, Friede & Maurer-Schultze, 1984) the effect of 200 mg/kg Ara-C consists of an inhibition of DNA synthesis and of killing a considerable portion of the L 1210 cells, predominantly of S phase cells. With respect to the importance for potential therapeutic regimens, the influence of the sequence and the time interval between the two therapeutic steps on the survival of tumour-bearing mice was studied. Most combination therapies significantly increase the survival of tumour-bearing mice compared to the single therapeutic steps; however, no significant differences between the various combined therapies were found. Whole-body X-irradiation with 4 Gy followed by the application of 200 mg/kg Ara-C 10 hr later resulted in the greatest increase of the mean survival time of tumour-bearing animals, from 13.2 to 17.4 days. It was shown that apart from the cytocidal effect on S-phase cells, Ara-C also kills cells sublethally damaged by a preceding X-irradiation.

Functional modifications of macrophage activity after sublethal whole-body irradiation.

The effect of whole body x-irradiation on macrophage activity was evaluated by in vitro C3b-receptor-mediated ingestion and in vivo carbon clearance. Peritoneal macrophages from B/sub 6/D/sub 2/F/sub 1/ mice were tested from 20 min to 24 hr postirradiation and at doses up to 1000 rad x-irradiation. When compared to peritoneal macrophages from normal unstimulated mice, whole-body irradiation produced an increase in macrophage activity in both C3b-mediated ingestion and carbon clearance. The enhancement of macrophage activity was optimal at an exposure of 200 rad and waned as the exposure dose increased. Enhanced activity appeared as early as 20 min postirradiation and peaked by 3 hr.

Effects of whole body X-irradiation and cyclophosphamide treatment on induction of macrophage tumoricidal function in mice

The influence of whole body X-irradiation (200–800 R) and subcutaneous cyclophosphamide (CY) treatment (150–500 mg/kg) was studied on the ability of adjuvants to induce cytotoxic macrophages in vivo. Surprisingly, radiation or CY therapy alone produced growth inhibitory macrophages whose function peaked within 2 days after treatment. When adjuvants such as Bacillus Calmette Guérin (BCG), pyran copolymer, or glucan were administered ip within 2 hr after sublethal (600 R) X-irradiation, adjuvant-induced cytotoxic function was depressed but not ablated. In addition, when noninduced peritoneal macrophages were obtained 6 days after lethal (800 R) X-irradiation, their ability to be activated in vitro by lymphokine or fibroblast-derived interferon preparations was only slightly depressed at all concentrations of inducer tested. When BCG, pyran, or glucan was administered ip concurrently with sc CY treatment, only the ability of BCG to activate macrophages was markedly reduced, indicating separate mechanisms for the induction of tumoricidal macrophages. A better understanding of the interaction of chemotherapeutic and/or radiation regimens with adjuvants which affect macrophage function may be instrumental to rationalized immunotherapy protocols.

Effects of Whole-Body X-Irradiation on Some Aspects of Collagen Metabolism in the Rat

Whole-body exposure of adult rats to X rays at sublethal or lethal doses causes a decrease in hydroxyproline levels in urine and skeletal muscle. Similarly, reduction in the excretion of labeled hydroxyproline in urine following intraperitoneal injection of ${}^{14}{\rm C}\text{-proline}$ , may be attributed to impaired in vivo hydroxylation of proline. Incorporation of administered ${}^{14}{\rm C}\text{-proline}$ into ${}^{14}{\rm C}\text{-hydroxyproline}$ and its distribution in different metabolic forms of collagen in skeletal muscle and skin are markedly reduced in X-irradiated rats. These suggest impaired hydroxylation of proline. However, in vitro proline hydroxylase activity in liver is not affected by radiation treatment. Decreased endogenous oxygen consumption, as observed in liver homogenates of X-irradiated rats, may be one of the factors which affect in vivo proline hydroxylation.

The Relationship of Strain, Sex, and Body Weight to Survival Following Sublethal Whole-Body X-Irradiation

Life-shortening effects of whole-body X-Irradiation of C3H, BALB/c, RFM, C57BL/6, ${\rm C}3{\rm CF}_{1}$, ${\rm B}6{\rm RFMF}_{1}$, and a four-way cross were compared. Male and female mice exposed to 300 R at 5-6 weeks of age showed significant life shortening in all strains and crosses. Females were, in general, 1.5 times more sensitive than males of the same strain, suggesting a constant effect of sex. There were substantial differences in sensitivity within the same sex among strains and it was found that this strain-specific difference was highly correlated with body weight at 6 weeks of age. On this basis a hypothesis has been advanced which views some of the strain-specific differences in radiation sensitivity as due to differences in maturational rate or to processes which are highly correlated with maturational rate.

Release of Ribosomes from Endoplasmic Reticulum (E.R.) of X-Irradiated Livers

MUKERJEE, H. AND GOLDFEDER, A. Release of ribosomes from Endoplasmic Reticulum (E. R.) of x-irradiated livers. Radiat. Res. 58, 253-261 (1974). The effects of whole-body x-irradiation on mouse liver cells were studied. At 1 hr after 2000 rad, the concentration of free ribosomes increased by 15-20% in post-mitochondrial fractions and by about 30% in post nuclear fractions. The release of ribosomes was accompanied by 47 % loss of Ca2+ and 17 % loss of Mg2+ in liver microsomal fractions. The activity of glucose-6-phosphatase in endoplasmic reticulum (E.R.) membranes of liver also decreased by 30% after 2000 rad. The loss of Ca2+ and Mg2+ and the decrease in the activity of the membrane bound glucose-6-phosphatase suggest a possible change in composition and structure of E.R. membranes after x-irradiation.

The Effect of Whole-Body X-Irradiation of Guinea Pigs on the Liver Ribonuclease and Ribonuclease-Inhibitor System

The purpose of the experiments was to reveal the contribution of ribonuclease (RNase) activity, the enrichment of the size and amount of polysomes, and to the enhancement of protein synthesis occurring in the liver after x-irradiation. The time dependence of RNase activity was studied between 2 and 30 hr after whole-body x-irradiation of guinea pigs with 3000 R. As found, RNase activity dropped to its minimum in deoxycholate (DOC)-treated liver microsomes at 15 hr. Accordingly, fewer polysomes degraded than in unirradiated controls, as shown by the size distribution of polysomes in the pattern obtained by sucrose density gradient centrifugation. The dose dependence experiments were performed at 15 hr after x-irradiation. In microsomes not treated with DOC the alkaline free RNase did not change appreciably up to 3000 R and the total alkaline RNase activity decreased slightly between 500 and 1500 R. In microsomes treated with DOC the free RNase activity decreased appreciably and the total RNase activity sli...

Effect of whole-body x-irradiation on plasma-protein synthesis: role of adrenals.

SummaryIn rats exposed to whole-body x-irradiation (800 R), the changes in plasma concentrations and glycine-1-14C incorporation into albumin, fibrinogen and total plasma proteins were followed for 6 days. In intact rats, the relative synthesis rate of fibrinogen showed two peaks at 3 hours and 4 days after irradiation (166 and 654 per cent of controls). In adrenalectomized and irradiated rats, this biphasic response was abolished and only a plateau was observed between 3 hours and 4 days. Adrenalectomized rats also showed a sharp rise in albumin synthesis 3 hours after irradiation. Thereafter, though it decreased progressively, it was more than that of adrenalectomized-unirradiated rats. The first peak (at 3 hours) of albumin and fibrinogen synthesis in adrenalectomized rats appears to be due to factors other than corticosteroids. Further, it appears that corticosteroids may not be the prime factors responsible for the elevated plasma protein synthesis in intact rats after irradiation. Since the magnitud...

Effects of Whole-Body X-Irradiation upon the Degradation of 14 C-Labeled Plasma Proteins in Intact and Eviscerated Rats

Plasma proteins labeled with ${\rm L}\text{-leucine-}1\text{-}{}^{14}{\rm C}$ have been given intravenously to adult male rats to study the effects of whole-body x-irradiation and the role of the gastrointestinal tract on catabolism of plasma proteins to14 CO2. Comparison of normal and irradiated eviscerated surviving rats reveals that substantial catabolism of ${\rm L}\text{-leucine-}1\text{-}{}^{14}{\rm C}\text{-labeled}$ plasma proteins to14 CO2 occurs in the absence of the liver, spleen, gastrointestinal tract, and pancreas. The overall effect of whole-body x-irradiation was to enhance the apparent extent of oxidation of14 C-labeled plasma proteins. Included for comparison are observations on the oxidation of a tracer dose or of a loading dose of ${\rm L}\text{-leucine-}1\text{-}{}^{14}{\rm C}$ in normal and irradiated eviscerated surviving rats.

Effect of whole body x-irradiation on the NP-SH level of blood in rabbits

Effect of whole body x-irradiation on the NP-SH level of blood in rabbits

Effect of Whole-Body X-Irradiation on Pulmonary Bactericidal Function

The mechanisms responsible for the enhanced pulmonary susceptibility to infection following x-irradiation are poorly understood. Since the intrinsic antibacterial mechanisms normally keep the lungs bacteria free, quantitative assessment was made in mice of the impact of sublethal x-irradiation on killing and removal of inhaled bacteria. Mice were irradiated with 500 R and exposed to aerosols of32 P-labeled Staph. aureus at 3, 10, 14, 21, and 31 days postirradiation. Measurements of pulmonary bacterial and radioisotope concentrations 0 and 4 hours after inhalation allowed calculation of the rates of both physical removal and intrinsic pulmonary bacterial killing. Electron microscopic studies of macrophages washed from the lungs, histologic studies of lung sections, and routine hemograms were also performed. Pulmonary bactericidal function was slightly decreased on day 14 and markedly decreased on day 21 (P < 0.01). Bactericidal function was not impaired 3, 10, and 31 days after irradiation. Physical remova...

Degradation and turnover of collagen in the mouse skin and the effect of whole body x-irradiation

1. 1. Male mice were given L-[ 3H]proline intraperitoneally at 4 weeks of age. The total radioactivity of hydroxyproline in the whole body skin increased with time up to the 6th week after the injection, and then gradually decreased to 19.8% of the peak value in the following 50 weeks. The half-life of the labeled skin collagen was calculated as 80 days in the mice at 18–30 weeks of age, 130 days at 30–45 weeks of age and 200 days at 45–60 weeks of age, respectively. 2. 2. The degredation of skin collagen in adult mice was accelerated by whole body exposure to a total of 900 or 1200 R X-ray. Exposure to 300 R 4 times resulted in a 30% increase in the degradation of labeled collagen in the 30–60-week-old mice. 3. 3. The total amount of collagen in the whole body skin was also significantly decreased by a total of 900 or 1200 R irradiation. 4. 4. The turnover rate of 1 M NaCl-soluble collagen was higher than that of insoluble collagen and this tendency was amplified by X-irradiation. 5. 5. The decrease in the solubility of skin collagen with ageing was accelerated by X-irradiation.

The Effect of Whole-Body X-Irradiation on the Median Lifespan of Female Dogs (Beagles)

The Effect of Whole-Body X-Irradiation on the Median Lifespan of Female Dogs (Beagles)

Effect of whole-body X-irradiation on tyrosine hydroxylase and catecholamine levels

Effect of whole-body X-irradiation on tyrosine hydroxylase and catecholamine levels

The Effects of Whole-Body X-Irradiation on Mouse Liver Alpha-Hydroxy Acid Oxidase

Mice were exposed to 800 R whole-body x-irradiation at a rate of 15 R per minute. Alpha-hydroxy acid oxidase activity was measured in the liver at various time intervals postexposure. The enzyme activity was increased at 24 hours postirradiation and returned to normal levels at 4 days postexposure. The intracellular distribution of alpha-hydroxy acid oxidase as determined by differential centrifugation remained unaltered after irradiation.