[en] X-ray computerised tomography (CT) was performed on the lungs of CBA and C57Bl mice at varying time intervals after 13 and 16 Gy irradiation to the whole thorax. With careful consideration of artefacts associated with lung cross-sectional area and breathing rate, the mean density of the lung was evaluated in Hounsfield units (CT number). In CBA mice, this parameter showed a biphasic increase in lung density with time from irradiation, corresponding to an early phase of radiation pneumonitis and a late phase dominated by pleural effusions. Reduced lung volumes were also seen during the late response and lung compression due to accumulations of pleural fluid is considered a major factor in these observations. C57Bl mice did not develop radiation pneumonitis but appeared to be equally responsive to later radiation-induced increases in lung density. The results obtained from CT-derived densitometry compared well with measurements gained from functional and survival endpoints. X-ray CT provides a sensitive and informative technique for assessing the extent of radiation injury to the mouse lung and is potentially useful for quantifying the counterpart in patients. (orig.)

[en] Engraftment of donor bone marrow in relation to total body irradiation (TBI) dose was studied in syngeneic (B6→B6), MHC-compatible (BALB.B→B6) and MHC-incompatible allogeneic (BALB/c→B6) murine bone marrow transplantation (BMT) models. The steep dose-response relationships show how engraftment is critically dependent on TBI dose, as well as the genetic disparity between donor and host. (author)

[en] The dissociation of early and late lung damage in mice and rats irradiated to the whole thorax and the timing of pneumonitis and effusive stages for each strain is schematically summarised. An early and isolated incidence of pneumonitis was observed only in CBA mice. The absence of a prominent fibrotic pathology in the lungs of these animals is also in accordance with the clinical counterpart where the radiation doses at which widespread pneumonitis can be acceptably tolerated are at or below the lower limits of fibrosis. An independent expression of pleural effusions and the strain-related variation in response time implicates radiation damage to a separate target cell population with perhaps genetically determined variations in cell turnover. (UK)

[en] Acute single and fractionated exposures were carried out at a fixed dose rate, 1 Gy min^-1, and exposure times therefore ranged from 10 to 28 min. For low dose-rate continuous irradiation, the overall treatment time (2, 4 or 8 h) was kept constant and the various test doses obtained by varying the dose rate. Rates ranged from 11.7 to 18.3 cGy min^-1 for the 2-h exposure, from 6.7 to 11.7 cGy min^-1 for the 4-h exposure, and from 3.7 to 6.7 cGy min^-1 for the 8-h exposure. Results confirmed (a) the marked dose-sparing effect of fractionation even over short time intervals, and (b) that still greater sparing is obtained by low dose-rate irradiation. (U.K.)

[en] The aim of this study was to investigate the effects of ⁶⁰Co irradiation delivered at high (HDR) and low (LDR) dose-rates on rat salivary gland function. Total-body irradiation (TBI; total doses 7.5, 10 and 12.5 Gy) was applied from a ⁶⁰Co source at dose-rates of 1 cGy/min (LDR) and 40 cGy/min (HDR) followed by syngeneic bone marrow rescue. The severity of salivary gland dysfunction for each dose-rate was dependent on total TBI dose in all parameters. LDR irradiation significantly enhanced increase of lag phase, while it tended to further decrease flow rate during days 0-3. At later times the reverse effect was seen with significant LDR sparing in most cases. Changes in [Na⁺] and [K⁺] showed similar trends; LDR had an enhancing effect for early damage; beyond day 3 it consistently produced less. It is concluded that early postirradiation changes in salivary gland function are probably predominantly caused by irradiation damage to membrane structures and are less the result of reproductive failure. Later changes in salivary gland function are probably mainly dependent on repopulation of surviving stem cells. (author)

[en] The protraction of total body irradiation (TBI) to a continuous low dose-rate (LDR) has been investigated for its effect on donor marrow engraftment in murine bone marrow transplant (BMT) models of varying histocompatibility. The data suggest that radiation damage repair during LDR irradiation in an immunocyte target cell population is mainly responsible for enhanced graft rejection thus rendering protracted TBI less effective for application in clinical allogeneic BMT. (Author)

[en] Irradiation of the mouse right or left hemithorax at 14 or 18 Gy produced a dose-dependent rise in breathing rate 16 weeks after irradiation without significant mortality. The measurement of breathing rate changes following right hemithoracic irradiation combined with the maximally tolerated dose of cytotoxic drug was assessed as a method for qualitatively detecting drug-irradiation interactions with either exacerbate pneumonitis or alter its time course. Cyclophosphamide at 100 mg/kg accentuated and accelerated the rise in breathing rate, culminating in early mortality. BCNU 30 mg/kg delayed the appearance of the radiation response. Busulphan 30 mg/kg appeared to be radioprotective, but this was shown to be due to the DMSO-containing vehicle. Doxorubicin 6 mg/kg had no effect when combined with right or left hemithoracic irradiation. Carboplatin 100 mg/kg, vindesine 4 mg/kg and vinblastine 4 mg/kg had no substantial effect upon the changes in breathing rate. (author). 33 refs.; 6 figs.; 2 tabs

[en] Multiple fraction experiments have been carried out to determine the response of mouse lung to repeated small doses of 240 kV X rays down to 150 rad/fraction using breathing rate and lethality to assess damage. Two experimental approaches were used to measure the effect of small doses in vivo: (1) multiple equal doses and (2) multiple priming doses followed by a large test dose. Analysis was performed using the multitarget two-component model and the linear test dose. The amount of repair was calculated as a function of either dose per fraction (F/sub R/) or total dose (F/sub rec/). Both F/sub R/ and F/sub rec/ increased with decreasing dose per fraction but the change in F/sub R/ was small. The advantage of F/sub rec/ was that it varied more rapidly with dose per fraction than F/sub R/, so that possible differences between tissue repair capabilities are more visible on plots of repair as a function of dose per fraction. F/sub R/ and F/sub rec/ both decreased with the level of single-dose isoeffect injury; thus neither parameter is acceptable for comparing repair capability of different normal tissues with widely differing single-dose end point levels. Beta/alpha values were calculated and found to be a more acceptable index of repair capability than either F/sub R/ or F/sub rec/ because unlike those two parameters, β/α varied little with level of damage. Beta/alpha values of 1.7 to 4.2 krad^-1 were obtained for both lung death and increased breathing rate and are clearly intermediate between the lower β/α ratios for acute reactions, i.e., skin and intestine, and the higher values for late reactions in kidney and spinal cord

[en] The measurement of breathing frequency as a functional end-point of radiation-induced lung injury in mice allowed two phases of damage to be discerned; the first was manifest at 12-20 weeks after irradiation, the second beyond 28 weeks. Anesthesia by pentobarbitone sodium or steroids gave significant radioprotection of the lung during the early pneumonitic phase. Addition of the hypoxic cell sensitizer misonidazole removed the protective influence of the anesthetics but did not sensitize the lungs of unanesthetized mice. No anesthetic protection was detected for the late response, showing evidence for dissociation between early and late lung damage. The degree of epilation was measured on the dorsal thoracic region of the same mice. Protection by anesthetics and its reversal by misonidazole was also demonstrated. These results provide a warning of potential hazards in the laboratory evaluation of chemical radiosensitizers. The use of anesthetics at the time of irradiation could lead to an exaggerated enhancement of normal tissue damage

[en] The radioprotective effect of WR-2721 has been studied in mouse lung after single doses of radiation. Using the breathing rate assay and lethality, radioprotection was assessed at monthly intervals between 3 and 18 months after irradiation during both pneumonitis and chronic fibrosis. The degree of radioprotection was greater for fibrosis than for pneumonitis using both assays. In replicate experiments, dose modifying factors (DMF's) ranging from 1.2 to 1.4 were obtained for pneumonitis and 1.5 and 1.6 for fibrosis. The differences in DMF's for the two phases of lung damage were significant. A difference in the time course of expression of damage was seen in both the breathing rate and lethality assays between mice irradiated with and without WR-2721: the damage ended sooner in the drug-treated mice. This difference is best explained by protection of all damage after 5 months by WR-2721. No evidence of drug toxicty was found. It was concluded that WR-2721 protects against chronic lung fibrosis caused by radiation at least as well as against the earlier appearing pneumonitis after single doses of radiation. Thus, if WR-2721 is dose modifying and if late tissue complications are dose limiting in clinical radiotherapy, then a therapeutic benefit would be obtained by the use of this drug in clinical radiotherapy, provided that the radioprotection of tumors did not exceed a factor of 1.5-1.6