Renal adenocarcinomas induced by N 4 4' fluorobiphenyl acetamide and their comparison with human renal adenocarcinomas
Chronic administration of N 4 4 fluorobiphenyl acetamide to rats results in the occurrence of renal adenocarcinomas within 1 yr following initiation of administration. These tumors arise from tubules in the cortex or outer stripe and occur following a series of apparently premalignant stages involving megalocytosis, small areas of hyperplasia, carcinoma in situ, and, finally, invasive carcinoma. The ultrastructural features of the neoplasms are very similar to those of the human in that microvilli, intra and intercellular canaliculi, small mitochondria, and numerous lysosomes are seen. Both the human and experimental tumors produce abundant basement membrane material. Histochemically, the tumors show a marked shift toward glycolytic metabolism compatible with their ultrastructure. Studies of the experimental neoplasms grown in vitro, either as monolayers on plastic dishes or in sponges, reveal that the pattern of growth and ultrastructure continues to resemble that of the tumor. Furthermore, transplantation studies indicate that even very small lesions in the rat kidney can be transplanted, suggesting that they are carcinomas in situ. Cytologically, as in the human, the smallest nodules resemble the invasive cancers. Sarcomas were not seen with this model, as compared with dimethylnitrosamine. The N 4 4 fluorobiphenyl acetamide model, therefore, appears to be highly satisfactory for studying the mechanism, cocarcinogenic effects, treatment, and prognosis of renal adenocarcinoma.
Trump, BF; Hinton, DE; Dees, JH
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