Adenocarcinoma of the kidney. IV. Electron microscopic study of the development of renal adenocarcinomas induced in rats by N-(4'-fluoro-4-biphenylyl)acetamide.

Ultrastructural features of various stages in the histogenesis of renal adenocarcinoma induced in F344 rats by the carcinogen N-(4'-fluoro-4-biphenylyl)acetamide (FBPA) are described. FBPA was added to the diet up to 48 weeks; animals were killed at intervals from 4 to 52 weeks. Characterized were foci of cellular alterations followed by foci of proliferation with dysplasia leading to solid and cystic lesions, carcinoma in situ, and finally, carcinoma. Other lesions included foam cell nodules. Alterations also were noted in distal tubules. By electron microscopy, subtle changes in some proximal tubule cells of the pars recta were noted by 4 weeks (foci of cellular alteration). By 12 weeks there was evidence of dedifferentiation and reduction of cell polarity, thickening of basal lamina, alterations in endoplasmic reticulum and mitochondria, and increases in residual bodies. Nuclei of these cells possessed large nucleoli. From 24 to 36 weeks foci of proliferation were seen and consisted of tumor cells arranged in solid and cystic configurations. In solid lesions (less than 3 mm), in addition to the above alterations, cells showed a microvillus brush border in unusual locations, small and irregular mitochondria, multiple Golgi complexes and basal lamina, and loss of cell polarity. From 36 to 52 weeks carcinoma in situ consisted of cells similar to tumor cells described above. In addition, intracellular canaliculi were present. Areas of tumor cell degeneration and necrosis also were seen. Cells of larger carcinomas (greater than 3 mm), also observed at this interval, were identical to those of carcinoma in situ. Calcification of necrotic debris was noted.