A BIOCHEMICAL STUDY ON COMPENSATORY RENAL ENLARGEMENT IN UNILATERAL NEPHRECTOMIZED RATS TREATED WITH MITOMYCIN C OR 5-FLUOROURACIL
1981 Volume 72 Issue 7 Pages 865-879
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1981 Volume 72 Issue 7 Pages 865-879
Effects of mitomycin C or 5-fluorouracil on compensatory renal enlargement after unilateral nephrectomy in rats were studied by analyzing patterns of changes in DNA, RNA and protein contents.
The remaining kidneys of rats following unilateral nephrectomy or sham-operated kidneys were removed on the 1st, 3rd, 5th, 7th, 10th and 14th day after the operation. Just after the operation, animals received intraperitoneal injections of either mitomycin C (0.292mg/kg body weight) or 5-fluorouracil (21mg/kg body weight). DNA, RNA and protein in cortical, medullas y and tubular fractions of the removed kidney were determined according to Burton's method, orcinol method and Lowery's method, respectively. The data were expressed as ratios of the values in the left kidney to those of the right kidney in each animal.
In the animals treated with mitomycin C or 5-fluorouracil, the increase in kidney weight after unilateral nephrectomy was similar to that of the untreated animals up to the 10th day, but significantly lower on the 14th day. The ratio of cortical weight to medullary weight, however, remained almost constant during the experimental period.
In the nephrectomized control rat, hyperplastic and hypertrophic responses were noticed in both cortex and medulla, as judged from patterns of increments in DNA, RNA and protein contents. However, hyperplastic response which was active between the 1st and 3rd day was somewhat stronger in the cortex than in the medulla. The effect of mitomycin C to the nephrectomized animals was characterized by severe suppression of hyperplasia in both cortex and medulla, and by remarkable decrease in DNA content on the 7th day, suggesting the presence of destructed nuclei. This decreased level of DNA content recovered rapidly after the 7th day. The hypertrophic response was not significantly impaired by mitomycin C. A single administration of 5-fluorouracil resulted in a remarkable suppression of hypertrophic response on the 1st day, and a slight decrease in hyperplasia on the 3rd day. Thereafter, no significant change was observed.
On the basis of the above results, clinical meanings of administration of antitumor drugs after nephrectomy were discussed.
