Der Einfluss der Dosisleistung auf die therapeutische Wirkung von ⁶⁰CO-Gammabestrahlung beim Adenokarzinom der Maus.

Transplantable adenocarcinomas of C3H-mice were irradiated with doses between 7 and 75 Gy, using a dose rate of 3.6 Gy/min, or with doses from 10 to 80 Gy using dose rates between 0.06 and 0.17 Gy/min a 60Co-gamma source. A radiation-induced delay of growth or the local cure were recorded. The relative effectiveness of irradiation of the tumor using a low dose rate decreases at first down to a value of 0.66 at 25 to 30 Gy, if the doses are increased; then, if the doses delivered are further increased, it mounts again to 0.88 when the median curative radiation dose is reached

Accelerated repopulation in tumours and normal tissues.

Accelerated repopulation is a well established response pattern of normal epithelial to fractionated irradiation. It is delayed until the tissue recognises functional injury. It is well regulated to maintain a steady state and continues until integrity of the tissue is restored. We assume that some of these features of the parental normal tissue are preserved and still operate in squamous cell carcinoma, although probably in a less well controlled and organised manner

Chronic radiation damage in the rectum of the rat after protracted fractionated irradiation.

In this experiment, a protracted fractionation regime (18 fractions/170 days, dose/fraction: 6,7,8 Gy) caused late rectal obstruction in rats independently of any clinically detectable acute damage. Rectal obstruction was due to an ulcer which developed secondary to an atrophic mucosa and capillary damage. In agreement with our earlier protracted fractionation schedules, the results were not fitted well by the linear-quadratic model. However, there are indications of relatively low alpha/beta values. Hydronephroses and hydroureters were the only competing risks to rectal obstruction and they occurred independently of it

Jejunal crypt stem-cell survival after fractionated γ-irradiation performed at different dose rates.

Jejunal crypt survival after fractionated total body irradiation of C3H mice given at dose rates between 1·2 and 0·08 Gy/min was studied and the results analysed according to the linear quadratic model. Whereas α was independent of dose rate β decreased with dose rate to approach zero at about 0·01 Gy/min. During the period of recovery, sublethal damage from doses given at high dose rate interact with low dose rate irradiation given immediately after, and increases its effectiveness

Endothelial cell proliferation in the rat heart following local heart irradiation.

Radiation-induced myocardial degeneration in the rat is preceded by changes in capillary structure and function, which may be a major factor in the pathogenesis of radiation-induced heart disease. In order to investigate the mechanism of capillary damage we studied endothelial cell proliferation in untreated control rats and in rats at different times following local heart irradiation with 20 Gy using [3H]thymidine autoradiography. Since the latency times of myocardial degeneration as well as capillary damage are about twice as long in Sprague-Dawley rats as in Wistar rats, endothelial cell proliferation was studied in both strains. The percentage of labelled nuclei (LI) after repeated labelling over a period of 12 h was 0·32 ± 0·06 in control animals of both strains. Therefore the turnover time of endothelial cells was estimated to be between 115 and 400 days. Following irradiation the LI increased above control levels. In both strains this was concurrent with the time of onset of capillary depletion and alkaline phosphatase loss, which occurred at around 23 days post-irradiation in Wistar rats and 58-74 days in Sprague-Dawley rats. In both strains the increase in LI was confined to alkaline-phosphatase-negative areas. In phosphatase-positive areas endothelial cell proliferation was unchanged in spite of the reduction in capillary density. Since, in general, the latency to post-irradiation death of a cell is closely related to its normal turnover time, the decrease in capillary density is not due to mitotic death of proliferating cells as is commonly seen in other tissues

Dose fractionation effects in low dose rate irradiation of jejunal crypt stem cells.

Jejunal crypt survival after fractionated total body irradiation of C3H mice given at dose rates of 1·2 or 0·08 Gy/min was studied. The fractionation effect was more pronounced at the high dose rate than at the low dose rate. Analysis of the data according to the linear-quadratic survival curve model yielded an αbeta; value at 1·2 Gy/min of 13·3 Gy and at 0·08 Gy/min of 96 Gy

Cell progression and radiosensitivity of T₁-prospermatogonia in wistar rats.

T1-prospermatogonia pass through a quiescent stage which lasts from before birth until day 4 after birth (p.n.). They progress into DNA synthesis and mitosis in two synchronous waves which are separated by 24 hours in the evenings of day 4 and 5. The first wave contains about 25 per cent of the total population, the second 75 per cent. The mean duration of S-phase is 10 hours, the mean duration of G2-phase is 4 hours. After irradiation, the capacity of T1-prospermatogonia to produce the normal number of proliferating and differentiating cells in the testes is reduced. During maturation, between day 21 post-conception (p.c.) and day 5 p.n. the radiosensitivity of T1-prospermatogonia decreases by a factor of over 5

Radiation induced heart disease in hypertensive rats.

Spontaneously hypertensive Wistar rats were given single doses of X rays to their heart. Irradiation decreased the blood pressure before any myocardial radiation damage was apparent. Male rats, which were more hypertensive than female rats, had a shorter survival time after local heart irradiation than female rats. Antihypertensive treatment with hydralazine did not increase the survival time. It is considered that myocardial hypertrophy is the cause of the increased susceptibility of spontaneously hypertensive rats to local heart irradiation

Clonogenicity of the progeny of surviving cells after irradiation.

The clonogenic potential of the progeny of irradiated cells was tested in vitro by replating irradiated cultures after various times, allowing between five and over 25 subsequent divisions to take place after irradiation. Whereas the plating efficiency of surviving Chinese hamster cells was not decreased, in C3H10T1/2 cells a dose-dependent but slight decrease in plating efficiency was observed even after the longest follow-up period. These data do not contradict the prevalent hypothesis in radiobiology that the proliferation potential of a colonogenic cell surviving after irradiation is not significantly different from that of a non-irradiated cell