Shirley Hornsey

The effect of hypoxia during irradiation on four-day death in mice given single and split doses of electrons.

Abstract Anaesthetised mice were exposed while anoxic to single or split doses of electrons, and the values of four-day (intestinal) LD50 were compared with those for mice treated similarly while breathing oxygen. The values of LD50/4 for single exposures were 2,810 and 1,010 rads respectively, i.e. the oxygen enhancement ratio was 2·8. When fractionated doses were given in about that ratio, the time patterns of the split-dose recovery curves referring to anoxic and oxic mice were the same. Values of the LD50/4 were measured for 12-hour fractionation. The first doses were 1,600 or 600 rads to mice breathing nitrogen or oxygen. Dose-effect curves were the same for both groups, whether the mice were breathing nitrogen or oxygen during the second series of doses. Values of the LD50 were 3,980 and 1,410 rads when both doses were given under nitrogen and both under oxygen. Thus the differences in LD50 for single and split doses were 1,170 and 400 rads, i.e. the increments were in about the same ratio as the OE...

Sublethal damage in cells of the mouse gut after mixed treatment with X rays and fast neutrons

The effect of combining X ray and neutron irradiations on cell survival in the mouse intestine has been investigated. The irradiations from the two beams were given within minutes or at most a few hours of each other when recovery from sublethal damage was not always complete. The results show that cells surviving the first dose of radiation have accumulated the same amount of recoverable sublethal damage regardless of whether that first dose was with X rays or neutrons. The rate at which the sublethal damage is shed is the same after X rays or neutrons. It is reasoned that there is less sparing of damage by fractionation of neutron dose compared with fractionation of X ray dose not because there is less recovery from sublethal damage after neutrons but because there is relatively more lethal damage; the recovery from any sublethal damage is the same as if it were from X rays. If X rays and neutron doses are separated by times long enough to allow the full repair of sublethal injury then the combined effect is simply additive.

Slow repair after X-rays and fast neutrons

Two of the most important known phenomena which influence the response of cells and tissues to fractionated doses of ionizing radiation are recovery from sublethal injury and repopulation of surviving cells. The first of these is usually reduced with high LET irradiation, whereas repopulation is thought to be the same after all types of irradiation. Recently another repair process has been postulated to occur between doses of radiation, but only in tissues for which the normal generation time is long (Field et al., 1976).

Differences in survival of jejunal crypt cells after radiation delivered at different dose-rates

Abstract A comparison of the effects of dose-rate on the acute intestinal syndrome measured by animal survival five days after whole-body irradiation and on cell survival of the epithelial cells of the jejunum measured by clone production after local irradiation show a close correlation between the two tests of radiation damage. The greater sensitivity of animals measured by death within five days of irradiation to higher dose-rates is observed at the cellular level also. Irradiation of adjacent segments of jejunum suggest that the dependence of sensitivity on dose-rate is inherent in the cells rather than due to a radiation-induced change in the “environment” of the cells.

The relative effectiveness of super- and orthovoltage X rays for intestinal damage in man and mouse: an apparent discrepancy and its explanation

Abstract The RBE for 8MV X rays relative to 250 kVp X rays was found to be 1 for damage to the mouse intestinal mucosa measured by jejunal crypt counts. This value is at variance with the RBE of about 0·85 observed for clinical tolerance of patients in irradiation of the abdomen. It is concluded that this difference in RBE observed in mouse and man is due to the overriding importance of changes in depth-dose distribution and of integral dose in the determination of clinical tolerance in man. Only when differences in dose distribution between a new radiation and the reference radiation are minimal can factors obtained from small rodents be applied to man.

Differences in the effect of hypoxia on the radiation sensitivity of the bone marrow and the intestine in mice

Abstract Oxygen enhancement ratios, OERs, are reported for the bone marrow tissue assayed by animal survival 30 days after wholebody irradiation or by endogenous spleen nodule counts 11 days after wholebody irradiation for TO female mice and by endogenous spleen nodule counts for F1 hybrid (C3H × C57B1) mice. For both strains of mice the OER was 2·0. This was shown to be different from the OERs obtained for intestinal tissues assayed by animal survival four days after wholebody irradiation. The OER for intestinal damage was 2·5–2·7. It is not known whether these differences in OER are due to differences in the response of the circulation of these tissues to hypoxia or to intrinsic differences in the radiosensitivity in the cells of these tissues.

THE EFFECT OF DOSE-RATE AND ANOXIA ON THE RADIATION-INDUCED LOSS OF MACROMOLECULES INTO THE INTESTINE.

Abstract The leakage into the gut in mice of molecules of 131I polyvinylpyrrolidone (P.V.P.) of the size of plasma protein molecules, has been measured after whole-body irradiation of animals whilst breathing oxygen or nitrogen. Irradiation was carried out using 8 MeV electrons and 250 kVp X rays. Results suggest that the protective effect of anoxia may be higher for this test of damage than for the acute intestinal syndrome, i.e., death at four to five days. The effect of changes in dose-rate seen for the four-to-five day death endpoint is not reflected in the measurements of leakage of 131I P.V.P.