Morphology and proliferation kinetics of early tumor stages induced by dimethylnitrosamine in rat kidneys

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Abstract
A total of 49 dimethylnitrosamine (DMN)induced rat renal cell tumors were analyzed and classified cytomorphologically at an early stage of development. Of these, 17 were basophilictubular tumors, two of which showed a direct transition to proximal tubules of the P3segment; 21 lesions were vacuolated and contained glycogen; these were defined cytomorphologically as a separate tumor type the histogenetic derivation of which from the collecting duct system was established by documentation of a direct transition. Morphological similarities point to the lipidstoring variant of the basophilic tumor, but a carcinoma of the ducts of Bellini is another possible human equivalent of this tumor type. Another seven lesions were clear and granular cell tumors. In two of these a direct transition from the collecting duct system was found, thus confirming that this only recently established origin of experimentally induced rat renal clear cell tumors also applies to lesions induced by DMN. The proliferation kinetics of DMNinduced lesions were studied in autoradiograms after pulselabeling with tritiated thymidine. The basal proliferation of these early tumor stages displayed a marked proliferative advantage over the normal parenchyma. The lesions were still subject to physiological growth stimulation as determined by3HTdRcontinuouslabeling with osmotic minipumps following unilateral nephrectomy. However, compared with normal kidney parenchyma, the3HTdRlabeling index of the lesions was even higher indicating a response modification during early neoplasia.
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