Cell Proliferation in the Murine Epidermis and Subcutaneous Vascular Endothelium after Hyperthermia

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Abstract
The skin of mouse legs was exposed to 44°C hyperthermia using a thermostatically controlled waterbath. Treatment at 44°C, for 15 or 30 min, led to oedema in the dermis immediately after treatment and to an infiltration by neutrophils within 7 h. The oedema disappeared in 2 days. Treatment for 60 min at 44°C led to subepidermal blistering and as a result of this a considerable area of the tissue became necrotic 4 days after treatment. A repair reaction followed, and 3 weeks after heating for 60 min at 44°C the epithelium was again completely or almost completely covering the underlying tissue. Shortly (7 h) after 15 or 30 min at 44°C an increase was observed in the number of basal cells in the epithelium incorporating [3H]thymidine. This increase declined slowly with time: 3 weeks after treatment the number of labelled basal cells was not significantly different from that in untreated skin. Shortly after 60 min at 44°C some basal cells of the epidermis still incorporated [3H]thymidine. The labelling index dropped to near-zero at day 2 after 60 min at 44°C. Thereafter repopulation started and in the areas next to the granulation tissue the labelling index of basal cells reached values close to 100 per cent, 2 or 3 weeks after treatment. Treatment for 15 min at 44°C did not lead to a stimulation of the proliferation of subcutaneous endothelial cells. Both 30 min and 60 min at 44°C led to a greatly enhanced proportion of labelled subcutaneous endothelial cells after 2 days and 4 weeks, respectively (labelling index between 35 and 40 per cent). After this peak value the labelling index declined rapidly. However, in granulation tissue it remained high for about 10 days after the peak on day 4. The stimulated proliferation of subcutaneous endothelial cells after heating for 30 and 60 min at 44°C correlated well with the finding that these heat treatments, given after or shortly before X-irradiation, led to a greatly reduced (X-ray-induced) tumour bed effect.