Ultrastructural study of the development of interstitial lesions leading to mesenchymal neoplasia induced in the rat renal cortex by dimethylnitrosamine
Within 24 hr following the administration of a single i_p. injection of dimethylnitrosamine in doses that result in up to 100% incidence of renal mesenchymal tumors, intracellular damage is seen with the electron microscope in interstitial cells with fibroblast morphology in the vicinity of glomeruli. Within several days of treatment, some periglomerular cortical fibrocytes and capillary endothelial cells are stimulated into division. An interstitial mononuclear inflammatory reaction, in which
... reaction, in which the macrophage is the dominant cell form, reaches a peak of intensity by 7 days. From 3 weeks on, a few glomerulus-associated hypercellular foci persist. The dominant cell type at this stage is the lymphocyte , although by 8 weeks plasma cells are also numerous. Abnormal fibroblast-like cells are noted in very small but increasing numbers within persisting lesions from 3 weeks after drug administration. By 12 weeks, there is a marked reduction ofimmunological cells, and persisting lesions consist predominantly of aggregations of fibroblast-like cells ultrastructurally identical with spindle or stellate cells of well-developed tumors. By 20 weeks, the proliferating lesions display the broad spectrum of vascular differentiation characteristic of these tumors. The findings are discussed with respect to the correlation between the target cell of acute injury and the ultimate development of neoplasm and the significance of abnormal cell forms present in early, persisting lesions.