Doses Of Total Body X-irradiation Research Articles

Sedimentation von nukleoiden aus thymus- und milzzellen der ratte nach ganzkörper-röntgenbestrahlung / Sedimentation of nucleoids from thymic and splenic cells of the rat following total-body x-irradiation

The sedimentation of nucleoids from thymic and splenic cells of rats was tested following totalbody X-irradiation (TBI) with doses ranging from 24 to 1520 cGy. The principal results may be summarized as follows: 1) The nucleoid sedimentation of the cells was reduced immediately after TBI with doses of ≥ 760 cGy. In the following postirradiation period, an enhancement of sedimentation rate has been observed which could be neutralized by addition of proteinase K to the nucleoid preparation. 2) When nucleoids were prepared 6 h after TBI with doses ≥ 190 cGy, beside the main nucleoid band a smaller nucleoid fraction appeared in the ethidium bromide containing saccharose gradient. This fraction was of less sedimentability than the main nucleoid peak and could not be distinguished from pure, high molecular DNA. - From the present results it is suggested that the reduction of the nucleoid sedimentation immediately following high doses of TBI is the result of primary (non-repaired) DNA lesions whereas the changes detectable some hours later are due to the secondary enzymatic changes connected with the interphase death of the cells. With respect to the detection of in vivo effects of X-irradiation, the nucleoid sedimentation has to be regarded much less sensitive than some biochemical and/or cytomorphological methods

The enhancing effect of cell-wall aggressin on the virulence of Staphylococcus aureus in normal and irradiated mice and in man.

Mice irradiated with lethal doses of total body X-irradiation are very susceptible to Staphylococcus aureus. A difference in virulence between a “mouse-virulent” strain and a “mouse-non-virulent” strain which lacks cell-wall aggressin could nevertheless be demonstrated. The virulence of the “mouse-non-virulent” strain could be increased by adding a cell-wall preparation with aggressin-activity (DOCR) from a “mouse-virulent” strain to the inoculum. When injected together with a dose of bacteria lower than the minimum pus-forming dose a lesion-enhancing effect of DOCR from a “mouse-virulent” strain was also demonstrated in man.

Effect of Chronic Gamma Radiation on Airborne Infection of Mice with Listeria monocytogenes

It is well known that exposure to a single acute dose of total-body X-irradiation within the midlethal range markedly increases the mouse's susceptibility to experimentally induced bacterial infection. In comparison, a paucity of information exists regarding the effects of continuous exposure to low doses of y-radiation. Hammond et al. (1) studied the effects of continuous exposure to low doses of 7yradiation on the susceptibility of mice to Pseudomonas infection. Animals exposed at rates of 69 and 128 r/day demonstrated an increased susceptibility to intraperitoneal challenge of the bacteria. At these levels, accumulated doses of 3845 and 2695 r, respectively, were obtained. Those exposed at 34 r/day accumulated 2140 r but showed no significant increase in susceptibility. A few deaths from the radiation alone were observed in the groups receiving 69 and 128 r/day, but none occurred among the mice exposed at 34 r/day. In a later study (2) the challenge inocula were graded by less than a tenfold dilution, as previously used, in an attempt to detect smaller changes in susceptibility. With this method it was shown that daily exposure to 15 r of y-radiation (1350 r accumulated) resulted in a slight but demonstrable increase in susceptibility to intraperitoneal inoculation of Pseudomonas. In the present study, accumulated radiation doses up to 2500 rads were obtained by continuous exposure at 24 to 34 rads/day. These levels of radiation exposure were

EFFECTS OF SINGLE AND FRACTIONATED DOSES OF TOTAL BODY X-IRRADIATION IN UTERO ON GROWTH OF THE BRAIN AND ITS PARTS.

Effects of Single and Fractionated Doses of Total Body X-Irradiation in Utero on Growth of the Brain and its Parts

Changes Induced in the Mouse Spleen by Graded Doses of Total-Body X-Irradiation

Albino Carworth Farms # 1 mice of both sexes, 12 to 14 weeks of age, bred in our own laboratory, fed Wayne Lab Blox ad libitum, were placed in perforated plastic tubes without anesthesia for x-irradiation exposure. X-Irradiation was with a 250-kvp therapy machine, 0.5 mm copper and 1.0 mm aluminum filtration. The target-to-mouse distance was 75 cm, and the radiation intensity was 32 r/min with a maximum variation of 5% within the field limits used. Radiation doses of 30, 50, 100, 150, 200, 250, 400, 500, 600, 800, 1000, and 1500 r were administered in a continuous dose. The animals were then returned to their cages and were sacrificed 24 hours later by decapitation with shears without anesthesia. The spleen was removed and weighed, and aliquots were subjected to DNA and acid DNase analyses as previously described (1, 2). Five to ten animals were used at each dose studied, and the results averaged. An equal number of animals, similarly handled, but not irradiated, served as controls for each point.

Delayed Effects of Multiple Sublethal Doses of Total Body X-Irradiation on the Periodontium and Teeth of Mice

Effects of multiple sublethal doses (6 weekly exposures of 200 r each) on the subsequent appearance of the periodontal and dental tissues were studied in male mice fed either a highly purified diet complete in all know nutrients or a natural food stock ration. Periodontal lesions were observed in x-irradiated animals on the purified diet 100 days following the 1st irradiation exposure, but not prior to this time. The subsequent development of the lesions generally paralleled that of primate periodontitis and was characterized by plaque formation, gingival recession, periodontal destruction, dental necrosis, and exfoliation. In contrast, no periodontal pathology was observed in xirradiated mice on the stock diet. Multiple sublethal x irradiation appears to be a primary etiologic factor in the formation of periodontal lesions in mice fed the purified diet. Secondary factors, such as age, diet, trauma, oral bacterial flora, heredity, may also be implicated. Two manifestations of radiation injury, namely, diminution of body resistance to infection and the so-called aging effect of radiation, should be considered too. Histologic studies indicated that salivary function, particularly of the palatal gland system, was impaired. Areas of fibrosis and reduced glandular tissue were prominent in several irradiated animals on the purified diet.more » This suggests a more specific type of radiation- induced somatic lesion, with its focus upon the oral environment. Impaired salivary function could play an important etiological role in the lesions observed, by facilitating the accumulation of plaque material. (H.H.D.)« less

Effects of source of dietary carbohydrate on survival time of sublethally x-irradiated mice.

SummaryExperiments were conducted to determine the effects of source of dietary carbohydrate on survival time of mice exposed to multiple sublethal doses of total body x-irradiation. Findings indicate that average survival time of x-irradiated mice was significantly longer on a glucose-containing diet than on rations containing sucrose, dextrin or cornstarch as the source of dietary carbohydrate.

Deleterious effects of high fat diets on survival time of X-irradiated mice.

The effects of multiple sublethal doses of total body x-irradiation were determined on survival time of male mice fed either a purified fat-free ration or a similar diet supplemented with 2, 10, 20, or 30% cottonseed oil, marganine fat, or butter fat. The effects obtnined were dependent on the amount and source of dietary fat. At levels of 2 or 10% of the diet, cottonseed oil and margarine fat increased survival time over that on the fat-free ration. When these fats were fed at higher levels (i.e., 20 or 30% of the diet), however, survival time was decreased below that obtained at the lower levels of supplementation. In contrast to the results obtained with the cottonseed oil or margarine fat supplements, butter fat at levels of 2 or 10% of the diet did not prolong survival over that on the fat-free ration; nor did it decrease survival time when fed at higher levels in the diet. (auth)

Further biochemical studies on male and female mice some months after total-body x-irradiation.

SummaryHigh doses of total-body x-irradiation produced a decrease in the fat content of the skin of female CBA mice examined some months after the exposure. The weights of the heart and kidneys were not different from the unexposed controls. The irradiation brought about a permanent depression in DNA-synthesis relative to RNA in the kidneys of both sexes.

Effects of Low-Fat Diets on Survival Time of Mice Exposed to Multiple Sublethal Doses of Total-Body X-Irradiation

The average survival time of mice exposed to multiple sublethal doses of total-body x irradiation was significantly less on a fat-free ration than on a similar diet supplememted with 10% cottonseed oil. Methyl linoleats when incorporated at a 1% level or desiccated liver at a 10% level in the fat-free ratio also increased survivaI of x-irradiated mice over that on the fat-free diet, but hydrogenated coconut oil at a 10% level of feeding was without protective effect. The active factor (or factors) in liver was present in the liver-fat fraction obtained by azeotropic extraction with ethylene dichloride. (auth)

Failure of AET to protect against testes injury in the x-irradiated rat.

Intraperitoneal administration of AET at a level of 300 mg/kg body weight prevented death, but not testicular injury, in rats exposed to a single lethal dose of total body x-irradiation.

Variations in cerebral electrical activity in cats after total-body x-irradiation

In cats with chronically implanted electrodes, hippocampus and amygdala consistently showed spike discharges immediately after relatively low doses of total body x-irradiation (400 r) and reticular arousal thresholds were transitorily decreased. Thalamic recruiting thresholds increased later, while hippocampal seizure thresholds remained practically unaltered. Experiments with lower doses are in progress.

Depression on Normal Serum Bactericidal Activity by Nitrogen Mustard

Summary Single intravenous injections of 2.5, 3.0 or 3.5 mg of nitrogen mustard/kg caused a depression in the bactericidal activity of rabbit serum against Bacillus subtilis. The loss of serum bactericidal activity did not take place until about the third post-treatment day and returned to normal between the 14th and 20th days after nitrogen mustard administration. An intravenous injection of L-cysteine immediately prior to the administration of nitrogen mustard decreased the length of time that serum bactericidal activity was depressed following nitrogen mustard treatment. Nitrogen mustard treatment caused no statistically significant difference in either the natural agglutinins against Bacillus subtilis or circulating complement. Both circulating leukocytes and serum properdin were depressed by doses of nitrogen mustard that suppressed serum bactericidal activity. The serologic alterations, leukocytic changes, and the depression of serum bactericidal activity which follows near-lethal doses of nitrogen mustard were almost identical to those that follow exposure to near-lethal doses of total body x-irradiation.

The Effect of Total-Body X-Irradiation on the Circulation of Splenectomized Dogs

Superficially the syndrome observed in dogs (1) after fatal X-irradiation resembles that reported in traumatic and hemorrhagic shock (2, 3). The circulatory changes in radiation shock, however, have not been so thoroughly studied as have those in other types of shock. To be sure, a fall in blood pressure has been observed in rats 2 to 5 hours after X-irradiation (4, 5), but this early change is not shown by dogs (6). In these animals large doses of irradiation which are fatal in 3 to 8 days produce a terminal reaction characterized by elevated body temperature, a rapid heart rate, and lowered blood pressure (7, 8). In the present study, the changes in the cardiovascular system (cardiac output, systolic and diastolic pressures, venous pressure, and heart rate), respiratory system (pulmonary ventilation, blood gases), and metabolism (02 consumption, C02 production, R.Q., body weight, food and water intake) were measured at intervals in splenectomized dogs, before and after exposure to lethal doses of total-body Xirradiation. These physiological changes were correlated with the clinical observations and pathological findings. A dosage of 1000 r was selected because the effects are reproducible, the survival time is predictable within narrow limits, and the course of the changes in blood volume is known (1, 9).

Effect of total body irradiation on absorption of sugars from the small intestine.

A study was made in rats on the effect of large doses of total body x-irradiation on the intestinal absorption of glucose, fructose and xylose administered intraduodenally. Irradiation caused a slight but highly significant decrease in absorption of all three sugars when given singly. These studies do not indicate selective inhibition of any specific mechanism involved in the absorption of these three sugars. No difference attributable to sex exists between the postirradiation absorption rates. When mixtures of the three sugars were given, a questionably significant decrease was noted in all absorption rates, with the exception of xylose in the female rats. In this group absorption of xylose was unaffected by irradiation. In rats not exposed to irradiation, the relative absorption rates of the three sugars are markedly different when given singly and when given in a mixture.

Effect of Various Doses of Total Body X-Irradiation on Total Amount of Deoxyribonuclease II in Rat Spleen.

SummaryThe increases in activity of spleen DNase II following a series of different doses of total-body x-irradiation 24 hours after treatment have been measured. These increases have been correlated with the change in spleen weights associated with the irradiation.

Neurological and EEG findings in the monkey after total body x-irradiation

Serial neurological and EEG examinations have been made in monkeys subjected to lethal and near-lethal doses of total body X-irradiation. With the onset of symptoms of radiation sickness, behavioral alterations consisting of anorexia, listlessness and hypokinesia appeared and, in severely ill animals, progressed to prostration and coma before death. Depression of iridal and tendon reflexes was encountered in such severely ill monkeys and, in one case, tic-like jerks of the neck and upper extremities were displayed terminally. In convalescent and surviving cases, no behavioral or neurological abnormalities were exhibited. Preliminary study of the normal monkey's EEG revealed low voltage fast discharge associated with alertness or excitement, an alpha rhythm of 7–9.5/sec. in relaxed wakefulness and large 1–2/sec. humps or waves with drowsiness or sleep. The induction of Nembutal anesthesia in the normal animal was associated with a period of low fast discharge before regular, high amplitude 1/sec. waves appeared. The overall EEG picture after irradiation was that of no significant change from normal. However, a slight slowing and greater irregularity of the alpha rhythm was present in several animals from the day of radiation. In pre-terminal stages, when the animal was severely ill, the EEG was greatly altered and consisted of high voltage, slow waves which gave way to an almost iso-electric tracing before death. These terminal alterations appeared secondary to general breakdown of the body's homeostasis, and the present findings are considered to be in accord with those of others which point to a high degree of resistance or protection of the nervous system to irradiation.

Thyroid response to total body x-irradiation.

DURING the past several years there have been many investigations into the effects of either total body or local x-irradiation on various mammalian organs. In the case of the thyroid gland, however, practically all of the studies undertaken have dealt with direct irradiation of the gland by local x-irradiation (Bender, 1948; Hursh et al., 1949) or by massive doses of radioactive iodine (Goldberg et al., 1950; Gorbman, 1950). These studies have shown that in the rat local irradiation of the thyroid produces essentially no change in morphology or function of that gland until the dosage reaches 3000–6000 r, a dose which is several times the magnitude of a lethal dose of total body x-irradiation. In a brief abstract, Evans et al. (1949), reported an increased uptake of I131 by the thyroid as well as “increased activity” in the blood of rats three days after 500–1000 r total body x-irradiation.

Local hemostasis in the hemorrhagic syndrome of irradiation.

IN AN EARLIER experiment 1 we demonstrated the efficacy of gelatin sponge in controlling local bleeding in the presence of the coagulation defect produced by controlled heparin and bishydroxycoumarin (dicumarol ® ) therapy. We had the impression that the fine mesh of interstices in gelatin sponge was responsible for the hemostasis, since the sponge was effective regardless of whether the fibrinogen phase or the prothrombin phase of coagulation was altered. In the present experiment we have produced a hemorrhagic syndrome in dogs with large doses of total body x-irradiation in order to test the effectiveness of gelatin sponge in controlling local bleeding in the presence of the complex coagulation defect due to irradiation. METHODS Sixteen mongrel dogs weighing from 6 to 9 kg. were used in this experiment. Dogs were dewormed and one week later subjected to total body irradiation, 2 350 to 400 r, while under intravenous pentobarbital sodium anesthesia.