Differences in survival of mouse colon crypts after whole- or partial-body irradiation.

The survival of mouse colon crypts after X-irradiation has been studied by the microcolony technique. The Do for crypt survival was 266 rad after whole-body irradiation in air, but when the colon alone was irradiated, the Do was 340 rad. In mice which were breathing 95 per cent oxygen, the Do values were 238 rad for whole-body and 302 rad for colon irradiation. The survival curves were all extrapolated to the same number, and the DQ was also increased with colon irradiation. There was, therefore an enhancement of colon crypt survival of about 27 per cent by local as opposed to whole-body irradiation. These results might be explained by a circulating repair promoter or by the production of a toxin after whole-body irradiation.     

Increased thromboxane production after whole body irradiation

Irradiation causes an increase in serum and plasma level of thromboxane in rabbits and an increase in thromboxane synthesis in blood platelets stimulated by thrombin. Thromboxane release from thoracic aorta is also increased upon irradiation of animals. H2O2 which stimulates thromboxane release from thoracic control aorta is without effect in the irradiated one.     

Depletion of glutathione after gamma irradiation modifies survival

The relationship between the intracellular glutathione (GSH) concentration and the aerobic radiation response was studied in Chinese hamster ovary cells. Various degrees of GSH depletion were produced by exposure to buthionine sulfoximine (BSO) and/or diethyl maleate (DEM). Diethyl maleate did not act as a classical radiosensitizer under the experimental conditions employed, nor did exposure to DEM/BSO nonspecifically affect protein thiols as measured by thiol blotting. Dose-response curves were obtained using cells irradiated in the absence or presence of DEM/BSO, which decreased GSH levels by 90-95%. Exposure to DEM/BSO did not affect the formation of DNA single-strand breaks or DNA-protein crosslinks measured immediately after irradiation performed at ice temperatures. Analysis of survival curves indicated that the Dq was decreased by 18% when GSH depletion occurred prior to, during, and after irradiation. The DEM/BSO exposure did not affect D0. To study postirradiation conditions, cells were exposed to 10 microM DEM prior to and during irradiation, which was performed at ice temperatures. Levels of GSH were depleted by 75% by this protocol. Immediately after irradiation, the cells were rapidly warmed by the addition of 37 degrees C growth medium containing either 10 or 90 microM DEM. Addition of 10 microM DEM after irradiation did not affect the degree of depletion, which remained constant at 75%. In contrast, GSH depletion was increased to 90% 10 min after addition of the 90 microM DEM. Addition of 90 microM DEM after irradiation produced a statistically significant difference in survival compared to addition of 10 microM DEM. In a second depletion protocol, cells were exposed to 100 microM DEM at room temperature for 5 min, irradiated, incubated at 37 degrees C for 1 h, washed, and then incubated in 50 microM BSO for 24 h. This depletion protocol reduced survival by a factor of 2.6 compared to cells not exposed to the combination of DEM/BSO. Survival was not affected if the cells were exposed to the DEM or BSO alone. This was interpreted to indicate that survival was not affected by GSH depletion occurring after irradiation unless depletion was rapid and sustained. The rate of repair of sublethal and potentially lethal damage was measured and found to be independent of the DEM/BSO exposure. These experimental results in addition to previous ones (Freeman and Meredith, Int. J. Radiat. Oncol. Biol. Phys. 13, 1371-1375, 1987) were interpreted to indicate that under aerobic conditions GSH depletion may alter the expression of radiation damage by affecting metabolic fixation.     

Increased radiosensitivity after irradiation of lymphocytes low adaptive doses

The variability of blood lymphocyte reaction on the adaptive irradiation (0.05 Gy at first, then 1.0 Gy 5 h later) was investigated by micronuclei assay. Blood samples were obtained from 700 children. It was shown that in all groups studied there were children with enhanced radiosensitivity ("radiosensitivity syndrome"-RS) after exposure to adaptive low dose of radiation. The radiosensitivity syndrome occurred more often in groups of ill children; part of them was characterized by the enhanced blood content of immunoglobulin E, enhanced level of T helpers and T suppressors. A high spontaneous level of lymphocytes with micronucleus is a factor of radiosensitivity formation. The possible factors resulted in radiosensitivity syndrome are discussed.     

Relation of the survival of irradiated dogs to the reserve of undamaged bone marrow

From the experiments with irradiated dogs it follows that the survival rate is a function of activity of bone marrow haemopoiesis which is in a good agreement with the previously proposed theoretical model.     

Skin graft survival after external beam irradiation.

Difficulties with skin graft ulceration after radiation therapy for cancer have led many to question the suitability of this method of soft-tissue coverage and its cost-effectiveness. The objective of this study was, therefore, to assess skin-graft integrity subjected to postoperative external beam irradiation in a rat model. The model consisted of a rectangular full-thickness skin graft raised and reapplied to its original bed on the dorsum of each rat. Five groups of adult male Sprague-Dawley rats (n = 8 per group) were established. Group A was the control group and was not given postoperative irradiation. Groups B, C, D, and E received postoperative unfractionated cobalt60 irradiation 4 weeks after grafting for a total dose of 15, 20, 25, or 30 Gy, respectively. Weekly skin-graft evaluation was performed for the 4 weeks after irradiation (8 weeks after surgery) by measuring areas of graft loss using computerized planimetry. After the animals were killed, histologic samples were obtained from normal unirradiated skin and from both intact and ulcerated skin-graft sites. Graft loss after irradiation of < or = 20 Gy was similar to that of the unirradiated controls. Occurring as early as 1 week after treatment, a two-fold increase in graft ulceration was observed with doses of > or = 25 Gy (p = 0.0007). Only partial healing of ulcerations was noted by the fourth week after treatment. Histologic changes associated with the irradiation of skin grafts using doses of 25 Gy or higher included hyaline degeneration, fibrinoid necrosis, telangiectasia, and edema. Granulation tissue predominated as a mechanism of healing in areas of graft ulceration. The intensity of inflammatory cell infiltrate did not correlate with radiation dose. The authors concluded that postoperative, unfractionated irradiation can induce skin-graft loss at doses of 25 Gy or higher. Fractionated irradiation or longer intervals between grafting and irradiation may increase skin-graft tolerance; however, further studies are warranted.     

Increased glomerular Vwf after kidney irradiation is not due to increased biosynthesis or endothelial cell proliferation.

Kuin, A., Citarella, F., Oussoren, Y. G., Van der Wal, A. F., Dewit, L. G. H. and Stewart, F. A. Increased Glomerular Vwf after Kidney Irradiation is not due to Increased Biosynthesis or Endothelial Cell Proliferation. Radiat. Res. 156, 20-27 (2001).Irradiation of the kidney induces dose-dependent, progressive renal functional impairment, which is partly mediated by vascular damage. It has previously been demonstrated that reduced renal function is preceded by an increased amount of von Willebrand factor (Vwf) in the glomerulus. The underlying mechanism and significance of this observation are unknown but, since it is an important mediator of platelet adhesion, Vwf in increased amounts could be implicated in glomerular thrombosis, resulting in impairment of renal function. Increased Vwf could be the result of increased biosynthesis by endothelial cells, or from increased numbers of endothelial cells after compensatory proliferation induced by irradiation, or it could be secondary to other events. In the present study, expression levels of mRNA for glomerular Vwf and glomerular cell proliferation rates were measured in control mouse kidneys and after irradiation with a single dose of 16 Gy. There were no significant changes in mRNA ratios for Vwf/beta-actin at 10 to 30 weeks after irradiation compared with unirradiated samples, whereas increased amounts of Vwf protein were seen in the glomeruli at these times. Labeling studies with IdU or staining for Ki67 demonstrated that glomerular proliferation was increased from 10 to 30 weeks after irradiation. Despite the increased proliferation rates, there was an absence of glomerular hyperplasia and no increase in the endothelial cell surface coverage in the glomeruli. Staining with antibodies against smooth muscle actin (SMAalpha) revealed that the observed proliferation mainly involved mesangial cells. These results indicate that the increased presence of glomerular Vwf after irradiation is not due to an increased number of endothelial cells per glomerulus, or to an increased production of Vwf. It is presumably secondary to other events, such as increased release of Vwf by damaged endothelial cells or entrapment of Vwf in the irradiated mesangial matrix.