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Biomedical subjects

J Denekamp

Publications and source records attributed to J Denekamp.

At least 181 records · Page 10Linked to original sources
PubMed1978

The effect of vascular occlusion on the thermal sensitization of a mouse tumour.

The effect of occluding the blood supply to a mouse tumour (with a metal clamp) has been studied for both irradiation and heating. Local heat was applied by immersion in a water bath for one hour at 42.8 degrees C or for 15 minutes at 44.8 degrees C. Occlusion of the blood supply during heating has a profound cytotoxic effect on the tumour, even in the absence of irradiation. Most tumours treated with 42.8 degrees C for one hour under clamped conditions were locally controlled whether they were irradiated or not. Tumours heated with their blood supply unobstructed showed a lesser sensitivity to heat, seen as an increased sensitivity to X rays with a thermal enhancement ratio of 1.8--2.6. With the shorter period of more intense heat (44.8 degrees C for 15 min), the effect of increasing the clamping time before heating was studied. The proportion of tumours locally controlled increased from 33% if the clamp was applied immediately before heating to 83% if the clamp was present for 60 minutes before heating commenced. No cures were observed for heat applied immediately before clamping, or immediately after release of the clamp. Accumulation of metabolic products or pH changes are implicated as the factors which alter the thermal sensitivity of these tumour cells.

Animals↗
PubMed1978

Sensitization of mouse tumours using fractionated X-irradiation.

The response of 3 different tumours to single doses and fractionated irradiation with and without misonidazole was compared. The osteosarcoma BS2 showed no significant drop in sensitization for 2 fractions compared with a single dose. The rapidly shrinking carcinoma NT and the non-shrinking fibrosarcoma showed a significant drop in the SER as the radiation dose was fractionated. This is consistent with effective reoxygenation occurring in both tumours. No sensitizing effect was observed in the fibrosarcoma for 5 fractions each given with metronidazole. When only 2 out of 5 fractions were given with the drug misonidazole, they were slightly more effective with the first 2 than with the last 2 fractions.

Animals↗
PubMed1977

Early and late radiation reactions in mouse feet.

The relationship between early and late radiation damage has been analysed by comparing the early skin reaction (desquamation in the first month) with the late foot deformity seen at 6 months, for mice from a wide variety of different fractionation experiments. A close correlation was observed between the early and late reactions in each experiment and the relationship was the same for all the experiments except for 17-64 fractions given over a short time. The fractionation schemes included single doses and 2-64 fractions, and the overall times ranged from 1 day to 6 months. This close correlation for such a wide variety of treatments suggests that the two end points are not necessarily independent responses of different tissues and that late damage in the mouse foot can result secondarily from depletion of the basal layer of the epidermis. Late foot deformity is therefore not a reliable model for the response of a slowly proliferating tissue.

Animals↗
PubMed1977

Sensitization of mouse skin to X irradiation by moderate heating.

The combined effects of heat and x irradiation have been studied on mouse skin using skin reactions on the feet. The skin was heated for one hour by immersion in a water bath at temperatures ranging from 25.5-43.5 degrees C. When the x irradiation was in the middle of this heating period a thermal sensitization to the x-ray damage was observed. The effect increased with temperature above 39.5 degrees C and doubled the effectiveness of the x rays at 43.5 degrees C. When the heating and irradiation were not concurrent the timing and sequence of treatments were important. Heat before irradiation was more effective than heat after irradiation, particularly if the interval was three hours or greater.

Animals↗
PubMed1977

Tumour regression as a guide to prognosis: a study with experimental animals.

An analysis has been made of the relationship between regression during therapy and the probability of local control in a group of mice treated with single doses and fractionated doses of X rays. The tumours were first generation transplants from spontaneous mammary carcinomas in C3H mice and were irradiated with single doses 3F/4 days, 9F/10 days, 9F/18 days or 15F/18 days. The size of the smallest radiation dose approached those encountered in clinical radiotherapy. A significant correlation was observed between the shrinkage during the treatment period and the local control at 150 days, for three of the four fractionated schedules. A weaker correlation was observed for shrinkage within a week after single doses, and for shrinkage during treatment with nine fractions in 18 days. It is postulated that the rate of shrinkage is an inherent characteristic of each individual tumour and does not reflect the number of cells killed. However, the shrinkage in some tumours during the course of therapy may result in more extensive reoxygenation which makes these tumours more sensitive to subsequent doses of fractionated course. The degree of shrinkage within the period of fractionated irradiation was found to be a useful prognostic guide to ultimate local control in individual tumours.

Animals↗
PubMed1976

Changes in the proliferation rate of mouse epidermis after irradiat-on continuous labelling studies.

The proliferative response of mouse skin to damage caused by X-irradiation has been tested by giving repeated injections of tritiated thymidine and scoring the percentage of labelled cells in high resolution autoradiography. Four, nine and fourteen daily fractions of 300 rads of X-rays were used and labelling commenced 4 days after the last fraction. The epidermis of the upper surface and the sole of the foot were scored separately and were compared with the skin of unirradiated feet. In unirradiated skin the proliferation rate of the basal layer cells is more rapid on the sole than on the upper surface. The cell cycle times deduced from continuous labelling curves were 81 hr and 111 hr respectively and the growth fractions were 97% and85%. After irradiation with small daily doses the homeostatic response to cell killing was slow. More rapid proliferation occurred after nine fractions in the sole, but was not apparent in the skin of the upper surface until fourteen fractions had been given. After fourteen fractions the cell cycle time was about 24 hr on both surfaces and the growth fraction was about 90%. The initial labelling index after a single thymidine injection was a poor measure of proliferation rate. The delay in the time of onset of faster proliferation is similar, both qualitatively and quantitatively, to that measured previously from the additional dose increments needed if large doses were given at different times after the multifraction treatments (Denekamp, 1973).

Animals↗
PubMed1975

Residual radiation damage in mouse skin 5 to 8 months after irradiation.

Residual injury from large doses of x-rays or neutrons given 5-8 months earlier was assessed by the response of the skin to further doses of 250 kV x-rays. The "dose remembered" was assessed by single test doses. Two doses separated by 24 hours or 7 days were given to assess the capacity for repair of sublethal injury and recovery by proliferation. About 10% of the pretreatment dose was "remembered" 5-8 months later. The capacity for repair of sublethal injury and proliferation was similar in controls and animals receiving 1000-3000 rads as pretreatment. These results apply to basal layer epidermal cells and may differ from those of more slowly dividing populations.

Animals↗