Polyethylene glycol as a protector against head and neck irradiation

Mice injected i.p. with polyethylene glycols (PEG) 20 min prior to head and neck X irradiation with 1650 rad showed improved survival, increased food and water consumption, and retention of body weight compared with irradiated controls. The LD $\text{50}\text{15}$ for PEG-treated mice was 1900 ± 108 rad compared to 1527 ± 56 for the controls. PEG of molecular weights 200, 400, and 600 afforded significant levels of radioprotection; PEG of molecular weights 1000, 1450, 4000, and 20,000 when given at maximum tolerated doses (～0.5 LD 50) did not. The degree of radioprotection by PEG with molecular 400 given 20 min before irradiation increased with dose up to the maximum tolerated dose of 6.4 g/Kg. Significant, but lower, levels of radioprotection were observed when the PEG was given 5 min after irradiation. Mice injected i.p. with PEG, cystamine, 5-thioglucose, chlorpromazine, polyethylene glycol monomethyl ether or polyvinylpyrrolidone all had comparable survival levels. Polypropylene glycol, polyethylene glycol diacrylate, and polycaprolactonediol were more toxic than PEG and showed no radioprotection.     

Effects of fast neutrons on rabbits-II. Comparison of pathologic effects of fractionated neutron and photon exposures of the lung and spinal cord.

Young adult rabbits were irradiated at high intensity twice weekly for 6 weeks to the cervical and thoracic spinal cord region (> 50% of lungs included in field); they were irradiated with photons (4 MeV) to 4 cumulative doses (from 4801) to 19,200 rad) or fast neutrons (15 MeV) to 4 cumulative doses (from 1680 to 6720 rad), with photon doses 2.86 times as large (assumed relative biological effectiveness) as corresponding neutron doses. The rabbits were observed especially for pulmonary and neurologic signs; when they became paralyzed or moribund, they were sacrificed for histopathologic study. Paraplegia occurred only after 6720 rad of photons or after neutron doses of 2520 rad or greater. Only in these rabbits were spinal cord lesions observed; they varied from occasional swollen axons to extensive necrosis and myelin loss, and were much more severe in the white than in the gray matter. Malignant bone tumors were found only in the irradiated field in 2 of the 3 rabbits receiving 2520 rad of neutrons. Radiation-induced lung changes were found in all irradiated rabbits, with the character of the lesions not depending upon dose but dependent on time after irradiation. Signs of severe respiratory diseases were seldom observed until just before death.     

Quantitative observations of the acute effects of X-irradiation on brain capillary permeability: Part I.

Rats were irradiated with single and multiple dally dose fractions of 200–2500 rad; the capillary permeability coefficients (P) for ¹⁴C-urea, ³H-galactitol, ³H-VM-26, and bleomycin were determined after completion of each course. The drugs have a wide range of molecular weights and lipophilicities.Radiation doses of 200 rad × 5 days and 400 rad × 1 day increased the urea P 14–32%, while other dose fractions had no effect on P. The P for galactitol was increased more consistently (52–116%) by single and multiple 200 rad fractions and single fractions of 400 and 1000 rad. The P for galactitol paradoxically was reduced approximately 60% by 200 rad × 10 days and 2500 rad × 1 day fractions. Permeability to galactitol was determined at various times 3–24 hr after single radiation doses of 200, 400, and 1000 rad; at all times P was increased over nonirradiated animals. No radiation dose had an effect on the P for bleomycin. Except for a single fraction (400 rad × 1 day), the P for VM-26 was also unaffected by radiation, and in that instance the P was reduced from normal.We conclude that the radiation fractions used in these studies produced little acute effect on the permeability of normal brain capillaries to the antitumor antibiotic bleomycin, the large lipophilic podophyllotoxin derivative VM-26, and urea, a small nonionized hydrophilic molecule. The only consistent increase in P occurred with galactitol, a hydrophilic molecule (molecular weight of 182 Daltons) that is normally quite restricted in its transcapillary transit in the brain.     

Post-irradiation lung density changes measured by computerized tomography

To investigate the possibility of using computerized tomography (CT) as a prognostic indicator of radiation induced lung toxicity, a series of CT scans were performed on one patient. These scans suggested an increase in lung density at day 73 after an upper half body irradiation. Because of the difficulty in lung density follow-up in patients irradiated for palliation, further studies were performed with LAF1 mice. Serial scans were taken on three groups of mice: (1) control group, (2) irradiated to 11.0 Gy and (3) irradiated to 14.0 Gy. Lung density increases between 10 and 15 were observed in the two irradiated groups. The time course was dependent on dose with an earlier onset for the high dose group (14 weeks) than for the low dose group (24 weeks). These density changes were observed only a few weeks prior to the death of the animals, indicating that small animals such as mice will not likely be useful for assessing CT scanning as an early predictor of radiation damage to lungs.     

Inhibition of artificial lung metastases in mice by pre-irradiation of abdomen.

A phenomenon by which pre-irradiation of the abdomen of mice reduced the lung-colony-forming efficiency of i.v.-injected tumour cells is described. The extent of lung-colony inhibition was shown to depend on both the dose and timing of abdominal irradiation. The maximum inhibitory effect was obtained when mice received 1200 rad gamma-irradiation to the abdomen 5--7 days before tumour-cell challenge, but there was no effect when abdominal irradiation was given 1 or greater than or equal to 14 days before challenge, or when radiation doses were less than 600 rad. In mice less than 3 weeks old, the effect was much less marked than in adults. The target tissue which, when irradiated, exerted the inhibitory influence on lung-colony formation was located in the ventral half of the abdomen in all 4 quadrants, and was probably gut. Radioactively labelled tumour cells were arrested normally in the lungs of irradiated mice, but were cleared more rapidly without evidence of sequestration in the irradiated gut. The most plausible mechanism seems to be that irradiation of the gut induces the production of natrual killer cells with anti-tumour activity, though this has not been conclusively established.     

Postoperative radiation therapy in lung cancer: A controlled trial after resection of curative design

Postoperative supervoltage radiotherapy was tested in a controlled clinical trial in an attempt to improve the survival for patients with bronchogenic carcinoma. Radiation therapy began 3 to 4 weeks after surgery; three fields were used giving a dose of 6,000 rad in six weeks to the mediastinum from a Co 60 unit. Between 1966 and 1975, 224 patients were included in this study. All had a resection of curative design. 175 patients were evaluable. No increase in survival time was noticed in the irradiated group. The 5 year survival rate was lower in this group (24% versus 43% for the control group) but the difference was not statistically significant. For squamous cell carcinoma, the analysis showed a detrimental effect of radiation therapy in the T 2 group (p < 0.05), this finding was significant, especially after pneumectomy (16 % versus 43 %). The slight benefit from radiation therapy was a decrease in local relapse (4 versus 19).     

Cell-cell matrix interactions in induced lung injury. II. X-irradiation mediated changes in specific basal laminar glycosaminoglycans

The thoraces of male LAF1 mice were irradiated at doses of 5, 9, or 13 Gy. The animals were killed at times of 1 hr, 1 day, 1 wk, 4 wks, and 12 wks postirradiation (PI). The lungs were removed, enzymatically or detergent digested, fixed with ruthenium red for demonstration of anionic sites, and processed for electron microscopy. Untreated (0 Gy, 0 time) and sham irradiated control groups were also processed. Sections of lungs were examined and changes in alveolar basal laminar anionic sites were quantitated. Changes in three groups of glycosaminoglycans (GAGs) were identified: chondroitin 4 and 6 sulfate-dermatan sulfate, hyaluronate, and other GAGs (principally heparan sulfate). At 1 hr PI, all groups showed a marked decrease in site number over controls, which continued to 1 wk. By 4 wks there was a marked relative increase in heparan sulfate containing sites for doses of 13 Gy and a moderate increase for the other doses. At 12 wks the level of heparan sulfate was considerably above normal for doses of 13 Gy and just above normal for the other doses. Chondroitin-dermatan sulfate had recovered by 12 wks for doses of 13 Gy, but was still subnormal for other doses; however, hyaluronate-containing sites recovered only slightly by 12 wks. The implications for this change on basal laminar permeability and the induction of fibrosis are discussed.     

Measure of blood flow by the multiple radioactive microsphere technique in radiated gastrointestinal tissue

In this study, two different radioactive microspheres were used to measure blood flow of an irradiated segment of small intestine in four dogs before, and 12 days after, irradiation with 2000 rad. The technique and implications are discussed. Using multiple radioactive microspheres, the study demonstrated an increased blood flow in irradiated tissues twelve days after a single dose of 2000 rad. There was also an increase in blood flow to adjoining nonradiated segments of intestine in the same animal. These observations may be of significance in clinical applications of radiation therapy and surgery. A major surgical concern is the impaired healing of irradiated tissue in the immediate postradiation period. The mechanism of this has generally implicated decreases in the perfusion of irradiated tissue. No decrease in blood flow was shown in this study, suggesting that other mechanisms, e.g., stem cell depletion, should be considered. Further studies of this type are recommended to increase understanding of the blood flow in irradiated tissue.     

Functional recovery in the irradiated kidney following removal of the contralateral unirradiated kidney

The right kidneys of seven Large White female pigs, approximately 14 weeks of age, were irradiated with single doses of 7-12.6 Gy of 250 kV X-rays. Sequential measurements of individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were carried out using 99mTc-DTPA and [131I]hippuran renography for time periods up to 24 weeks after irradiation. From this data, kidneys receiving a dose of 7 Gy were found to be functioning (F), while kidneys which received greater than or equal to 8.8 Gy were assessed as having no significant function (NF). When the pigs were approximately 10 months of age the contralateral unirradiated kidney was removed; the left kidney of three age-matched unirradiated pigs was also removed. The response of the right kidney to unilateral nephrectomy (UN) in these animals was assessed in terms of changes in haemodynamics (i.e. GFR and ERPF) for periods up to 24 weeks after UN. At post-mortem, the length and weight of the remaining kidney was measured. A marked increase in renal length was observed in irradiated kidneys following UN. In addition, the weights of irradiated kidneys following UN were greater than those of irradiated kidneys in age-matched pigs where the unirradiated kidney had not been removed. Four weeks after UN there was a pronounced increase in GFR and, in particular, ERPF in previously NF irradiated kidneys. The mean increase in these parameters, measured at the end of the follow-up period, when compared with the pre-surgery values, was 350.1 +/- 84.3 and 781.8 +/- 151.0% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Decrease in interleukin 2-induced vascular leakage in the lungs of mice by administration of recombinant interleukin 1 alpha in vivo

The administration of interleukin 2 (IL-2) to mice and humans is limited by the induction of a dose-dependent increase in vascular permeability causing a vascular leak syndrome (VLS). We have investigated the impact of the injection of recombinant interleukin 1 alpha (IL-1 alpha) on the VLS induced by IL-2 by measuring the extravasation of 125I-albumin into tissues and by assessing wet and dry lung weights. IL-1 alpha alone did not induce any significant extravasation of radiolabeled albumin. IL-2 alone, however, caused a significant increase in the extravasation compared to control lungs. IL-1 alpha injection along with IL-2 significantly reduced the IL-2-induced extravasation of radiolabeled albumin [9,886 +/- 533 (SEM) cpm were observed in IL-2 and IL-1 alpha-treated lungs compared to 14,172 +/- 2,628 cpm in lungs treated with IL-2 alone (P less than 0.02)]. IFN-alpha in combination with IL-2 produced more severe vascular leakage than caused by IL-2 alone. IL-1 alpha also significantly decreased (P less than 0.05) the vascular permeability induced by the combination of IFN-alpha and IL-2. We observed 44,811 +/- 13,131 cpm in IFN-alpha- and IL-2-treated lungs compared to 18,350 +/- 2,622 cpm in IFN-alpha-, IL-2-, and IL-1 alpha-treated lungs. The IL-2- and IFN-alpha-induced increase in lung water weight was also reduced significantly by the addition of IL-1 alpha. The decrease in vascular leakage was dependent on the dose and timing of IL-1 alpha administered. When recombinant IL-1 alpha was given as a single i.p. injection, 24 h before the injection of IL-2 (or Hanks' balanced salt solution) or IL-2 and IFN-alpha no abrogation of the VLS was observed. Although IL-1 alpha decreased VLS significantly in mice treated with IFN-alpha and IL-2 the survival of mice was not improved by the simultaneous administration of IL-1 alpha. Histologically, treatment with IFN-alpha and IL-2 produced marked perivascular and intraalveolar edema which was completely eliminated by the addition of IL-1 alpha. However, some perivascular edema in IL-1 alpha-treated mice remained which was equivalent to that caused by IL-2 alone. Treatment of MCA-106 induced pulmonary metastases was enhanced by the administration of IFN-alpha and IL-2 together.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prevention of Lung Metastasis by Intra-tumoral Injection of Cepharanthin and Staphylococcal Enterotoxin B in Transplantable Rat Osteosarcoma

The antitumor effect of intra-tumoral injection of Cepharanthin, a biscoclaurin alkaloid extracted from Stephania cephalanta Hayata, and staphylococcal enterotoxin B was evaluated using F344 male rats bearing transplantable rat osteosarcoma, S-SLM. A macroscopic lung metastatic nodule of tumor was transplanted into the subcutaneous back space, and 0.5 mg of Cepharanthin and 2 pg of staphylococcal enterotoxin B were injected into the tumor on days 12, 13 and 14. On day 28, all animals were killed with an overdose of pentobarbital sodium, and the transplanted tumors and lungs were examined. The wet weight of the lungs of the rats treated with Cepharanthin and staphylococcal enterotoxin B was significantly lower, and apoptosis in the lung metastatic nodules was significantly higher than that of the control or that of rats treated with only Cepharanthin or staphylococcal enterotoxin B. In the transplanted tumors, infiltration of TRAP (tartrate-resistant acid phosphatase)-positive multinucleated giant cells was prominent in the rats treated with Cepharanthin and staphylococcal enterotoxin B. These findings indicate that intra-tumoral injection of Cepharanthin and staphylococcal enterotoxin B induced infiltration of TRAP-positive multinucleated giant cells within the transplanted rat osteosarcoma, and reduced lung metastasis.     

Effect of vitamin A on lung tumorigenesis in irradiated and unirradiated strain A mice

The effect of vitamin A (retinyl acetate) on lung tumor development in strain A mice exposed to radiation was assessed. Four groups of 75 mice were utilized. Two groups were fed a low vitamin A diet (less than 100 IU/100 g diet) and the other 2 were fed a high vitamin A diet (800 IU/100 g diet). After 2 weeks one group maintained on the high vitamin A diet and one group maintained on the low vitamin A diet were given an acute dose of 500 rad of gamma radiation to the thoracic region. Circulating levels of plasma vitamin A in all 4 groups of mice were monitored. A difference in circulating vitamin A in the mice maintained on high and low vitamin A diet became evident by 20 weeks and continued for the duration of the experiment. Mice were killed 18, 26 and 40 weeks post-irradiation, their lungs were removed and the number of surface adenomas were counted. There was a significant increase in the number of mice bearing lung tumors and the mean number of lung tumors per mouse in the irradiated group maintained on the high vitamin A diet at 40 weeks post-irradiation as compared to the irradiated group maintained on a low vitamin A diet. Under the conditions of this experiment the development of pulmonary adenomas in irradiated strain A mice appears to relate directly to circulating levels of vitamin A.     

Comparative growth of SJL/J lymphomas in irradiated and normal SJL/J mice: cell cycle distribution and tumor cell quantification

Flow cytometric and biological quantification of tumor cells revealed that 650 rad gamma-radiation 1 day prior to iv injection of H-2Ds negative lymphoma cells into SJL/J mice resulted in approximately a fourfold (day 3) to twelvefold (day 7) decrease in the tumor cell content of lymphoid organs as compared to that in unirradiated mice. Approximately 1.6-fold less tumor growth was noted (day 7) in 700-rad gamma-irradiated as compared to growth in unirradiated (SJL/J X CBA/J)F1 mice. Distributions of tumor cells in S-phase of the cell cycle were comparable at days 3, 5, and 7 in irradiated and unirradiated mice. Although approximately 26% of splenic tumor cells were in S-phase at days 5 and 7 in irradiated SJL/J mice, splenic tumor cell content did not increase during this time period. The data indicate that early (prior to day 3) and late (after day 5) events are responsible for decreased tumor growth in irradiated mice.     

Effects of single-dose and fractionated cranial irradiation on rat brain accumulation of methotrexate

The effects of single-dose and fractionated whole-brain irradiation on brain methotrexate (MTX) has been studied in a rat model. The amount of MTX present in the brain 24 hr after a single i.p. dose (100 mg/kg) was the same wether animals were sham irradiated or given a single dose of 2000 rads 6 or 48 hr prior to the drug (6.9, 8.3, and 6.8 pmol MTX/g, wet weight, respectively). Animals sham irradiated or given 2000 rads in 10 fractions over 11 days and treated with an average dose of 1.2 mg MTX/kg i.p. twice a week for 24 weeks did not differ significantly in their brain MTX concentration (7.9 and 8.3 pmol MTX/g, wet weight, respectively). Chronically MTX-treated animals became folate deficient whether they were irradiated or not (450 and 670 pmol folate/g, wet weight, brain in MTX-treated and control animals). Thus, MTX accumulates in the brain with acute or chronic administration, and this accumulation is not altered by this amount of brain irradiation.     

Mapping metabolic changes associated with early Radiation Induced Lung Injury post conformal radiotherapy using hyperpolarized C-pyruvate Magnetic Resonance Spectroscopic Imaging

Purpose

Radiation Pneumonitis (RP) limits radiotherapy. Detection of early metabolic changes in the lungs associated with RP may provide an opportunity to adjust treatment before substantial toxicities occur. In this work, regional lactate-to-pyruvate signal ratio (lac/pyr) was quantified in rat lungs and heart following administration of hyperpolarized ¹³C-pyruvate magnetic resonance imaging (MRI) at day 5, 10, 15 and 25-post conformal radiotherapy. These results were also compared to histology and blood analyses.

Methods

The lower right lungs of 12 Sprague Dawley rats were irradiated in 2 fractions with a total dose of 18.5 Gy using a modified micro-CT system. Regional lactate and pyruvate data were acquired from three irradiated and three age-matched healthy rats at each time point on days 5, 10, 15 and 25-post radiotherapy. Arterial blood was collected from each animal prior to the ¹³C-pyruvate injection and was analyzed for blood lactate concentration and arterial oxygen concentration (p_aO₂). Macrophage count was computed from the histology of all rat lungs.

Results

A significant increase in lac/pyr was observed in both right and left lungs of the irradiated cohort compared to the healthy cohort for all time points. No increase in lac/pyr was observed in the hearts of the irradiated cohort compared to the hearts of the healthy cohorts. Blood lactate concentration and p_aO₂ did not show a significant change between the irradiated and the healthy cohorts. Macrophage count in both right and left lungs was elevated for the irradiated cohort compared to the healthy cohort.

Conclusions

Metabolic changes associated with RP may be mapped as early as five days post conformal radiotherapy. Over the small sample size in each cohort, elevated macrophage count, consistent with early phase of inflammation was highly correlated to increases in lac/pyr in both the irradiated and unirradiated lungs. Further experiments with larger sample size may improve the confidence of this finding.     

Cytological studies of esophageal carcinoma and gastric carcinoma receiving radiation and chemotherapy

The cytology of the endoscopic biopsy materials from 85 cases of esophageal cancer were analyzed for effects of the combined radiotherapy with Bleomycin. Cancer cells were remarkably decreased in number after the combination therapy. Unaffected cancer cells declined to negligible levels in 64 of 79 esophageal cancer cases irradiated more than 6,000 rad. Out of 42 gastric cancer cases treated with only anticancer drugs, 37 cases exhibited hardly cytologic changes in the smears of biopsied materials. About the remnant 5 cases, cancer cells showed partially cytoplasmic swelling, nuclear enlargement and nuclear abnormal stain. The smears of the biopsy and resected specimens from 64 gastric cancer cases with radiation and chemotherapy were cytologically discussed. The combination therapy increased the amount of both necrotic materials and neutrophils in the smears. The cytoplasms of treated cancer cells were swollen, vacuolated and stained abnormally. The nuclei of cancer cells became enlarged, multiple, piknotic and/or stained pale. Nuclear swelling was more prominent in cancer cells of differentiated adenocarcinomas. Cancer cells were decreased in number almost in inverse proportion to irradiation dose. Unaffected cancer cells were disappeared in 13 of 24 cases irradiated more than 6,000 rad, in 7 of 35 cases irradiated in the range 3,000 to 6,000 rad, in none of 5 cases irradiated less than 3,000 rad.     

Once-a-week irradiation for locally advanced lung cancer

Twenty-eight patients with very advanced lung cancer were treated with 500 rad once weekly to a total dose of 6000 rad (2050 ret). Twenty-one of the 28 patients (75%) achieved at least a partial local response. There were 9 patients (32%) who achieved a complete response and 12 patients (43%) who achieved a partial response. The responses were 9/11 for squamous cell carcinoma, 5/10 for adenocarcinoma, 5/5 for large cell carcinoma, and 2/2 for small cell carcinoma patients. Treatment was very well tolerated and in fact, no acute radiation related complications were observed during the 10-12 week treatment duration. Radiation induced fibrosis of various degrees has occurred but it has been mostly asymptomatic and similar to what is normally seen using conventional continuous schedules. In this group of very advanced lung cancer patients, failures have mostly resulted from metastatic progression; only one patient progressed locally in the irradiated field without evidence of metastatic disease. A preliminary analysis indicates that this treatment yields results that are similar to those achieved with conventional fractionation regimens and should be explored further.     

CFTR 对大鼠急性肺动脉梗塞时急性肺损伤的调节作用

目的：探讨CFTR对大鼠急性肺动脉栓塞时急性肺损伤肺脏水清除率的影响。方法：SPF级sD大鼠30只,建立大鼠左肺急性肺动脉阻塞模型。随机分为对照组,急性肺动脉梗阻4h和24h组,每组10只,分别测定左右肺的肺水容量,肺水清除率（AFC）,应用CFTR激动剂和抑制剂进一步调节发生变化的肺水清除能力,real—timePCR方法测定CFTR蛋白mRNA在大鼠肺组织的表达。结果：急性肺动脉阻塞4h和24h组的左肺肺水清除率（AFC）明显升高,肺动脉阻塞24小时后,肺水容量上升。但保持血液灌流的右肺无明显变化。CFTR激动剂NS004调节阻塞的左肺,各组肺水清除率升高不明显,但是CFTR特异性抑制剂CFrR—inhl72可降低各组已经升高的肺水清除率。Real—timePCR证实4h和24h组的左肺CFTRmRNA水平轻度升高。结论：CFTR可能参与在大鼠急性肺动脉栓塞时肺水清除率的变化。     

The density of mouse lung in vivo following X irradiation

The lungs of mice were irradiated with single X radiation doses of 5 to 14 Gy. Six weeks after irradiation, computed tomographic (CT) scans of the mice were performed at two-week intervals. Beyond 14 weeks after irradiation, the animals were scanned at 1-week intervals. The mice irradiated to 5 and 7 Gy exhibited no change in lung density, in comparison with the unirradiated lungs of control mice up to times of 48 weeks. The mice irradiated to doses of greater than 10 Gy exhibited marked increases in lung density at 15 weeks after irradiation. Increases in density followed a similar time course for these doses, but the magnitude of the density increase was dependent on the radiation dose. An interpretation of these findings in terms of radiation pneumonitis is presented, and the possibility of using Or to monitor lung density in radiotherapy patients is discussed.     

Tolerance of canine anastomoses to intraoperative radiation therapy

Radiation has been given intraoperatively to various abdominal structures in dogs, using a fixed horizontal 11 MeV electron beam at the Armed Forces Radiobiologic Research Institute. Animals were irradiated with single doses of 2000, 3000 and 4500 rad to a field which extended from the bifurcation of the aorta to the rib cage. All animals were irradiated during laparotomy under general anesthesia. Because the clinical use of intraoperative radiotherapy in cancer treatment will occasionally require irradiation of anastomosed large vessels and blind loops of bowel, the tolerance of aortic anastomoses and the suture lines of blind loops of jejunum to irradiation were studied. Responses in these experiments were scored at times up to one year after irradiation. In separate experiments both aortic and intestinal anastomoses were performed on each animal for evaluation of short term response. Response was graded by arteriography, gastrointestinal roentgenography, blind loop bursting pressure, and pathologic findings at autopsy and microscopic evaluation. The dogs with aortic anastomoses showed adequate healing at all doses with no evidence of suture line weakening. On long-term follow-up one animal (2000 rad) had stenosis at the anastomosis and one animal (4500 rad) developed an arteriovenous fistula. Three of the animals that had an intestinal blind loop irradiated subsequently developed intussusception, with the irradiated loop acting as the lead point. One week after irradiation, bursting pressure of an intestinal blind loop was normal at 3000 rad, but markedly decreased at 4500 rad. No late complications were noted after the irradiation of the intestinal anastomosis. Thus, it appears that adequate healing can take place with minimal risk of suture line breakdown even after a high single dose of irradiation (up to 3000 rad) to an anastomotic site. No late complications were observed after irradiation of intestinal anastomoses, but one needs to be cautious with regards to possible late stenosis at the site of an irradiated vascular anastomosis.