[Influence of Uremia on the Proliferation Kinetics of a Solid Transplantable Carcinoma (author's Transl)]

Unlabelled: Previous autoradiographic investigations revealed an impaired regeneration of epithelial tissues in acute experimental uremia. It was the aim of the present study to get information about the effect of uremia on the growth and the proliferation kinetics of a solid tumor (mammary carcinoma HB).

Material And Methods: The partly differentiated mammary carcinoma HB (Dr. C. W. Friis/Ry/Denmark) was examined in adult female mice (C3H/Tif). Acute renal failure was induced by ligation of the right ureter and by infarction of two thirds of the left kidney. A group of animals served for urea estimation during the first 7 postoperative days. A sham operation was performed in a control group. A starvation effect was avoided by additional tube feeding. Hemoglobin levels and reticulocytes were estimated in tumour bearing uremic mice and in a control group to get information about anemia in acute uremia. Calculating the tumour volume as a sphere with the geometrical mean of two diameters the tumour doubling time was derived from the growth curve. The autoradiographic experiments started on the 21th day after transplantation of the tumour (= 7th day after experimental uremia and sham operation respectively). The cell cycle was determined by the method of percentage of labeled mitoses. The growth fraction was estimated by continuous labeling method. For details of autoradiographic techniques see Fíaux de Lacroix et al. (1973.

Results And Discussion: During the first 48 hours the blood urea increased to more than 230 mg% and then decreased to a level of about 133 mg% at the 7th postoperative day. The blood urea of control animals was in the range of 50 mg%. Tumor bearing mice revealed an anemia (Hb: 8.1 +/- 1.2 g%, reticulocytes 60.1 +/- 36.5%) but no significant differences in hemoglobin levels and reticulocytes counts could be detected in uremic animals (Hb 9.7 +/- 1.7 g%; reticulocytes 31.4 +/- 11.6%). The growth of the tumour was impaired by uremia. The tumour doubling time was prolonged from 7.5 days in untreated and sham operated animals to 15 days in uremic mice. This was mainly due to a lowered growth fraction (from about 50% to 20%), and on the other hand to a prolongation of the generation time (from 15.5 to 19 hours) mainly caused by a prolonged Tg1-phase. The cell loss factor remained constant (about 81% in every group). Our findings in the transplantable solid tumour of uremic mice were similar to the results observed in the epithelium of the stomach, the intestine and of the skin as well as in erythroblasts especially in regard of the changes of the cell cycle. These observations in various tissues suggest a generally impaired cell proliferation in uremia.