Morphologic and Biologic Correlation of Lesions Obtained in Hepatic Carcinogenesis in A × C Rats Given 0.025 Percent N-2-Fluorenyl-diacetamide

Summary

A high correlation was found between the morphological interpretation and biological behavior of hepatic lesions induced by carcinogen feeding to rats. Inbred A × C male or female rats were fed 0.025 percent N-2-fluorenyldiacetamide in a semisynthetic diet for 2, 2½, 3, and 4 months; laparotomy, liver biopsy, and transplantation were carried out every 6 to 8 weeks. Autologous and isologous transplants of normal and cirrhotic liver and areas and nodules of hyperplasia (with a single exception) did not grow. A few “small hepatomas,” morphologically comparable to “carcinoma in situ” and measuring 5 mm or less in diameter, also failed to grow. Hepatomas that grew measured a minimum of 7 to 9 mm in diameter. Almost all primary hepatomas 1 cm or more in diameter grew autologously and isologously in transplant. Such well-developed hepatomas occurred only in animals given carcinogen for 3 or 4 months. To determine the transplantability the animals with transplants were followed for a number of months. The time of appearance of palpable growth, the rate of growth of the transplanted tumors, and the metastases were partly dependent on the morphologic pattern. Subsequent transplants of both well and poorly differentiated tumors appeared earlier in the second through the eighth generations. Pulmonary metastases were present in 26 percent of animals bearing successful transplants; 10 percent of these metastatic tumors were well differentiated and 90 percent were poorly differentiated. Curiously, well-differentiated hepatomas, 7 mm or greater in diameter, from rats given carcinogen for 4 months were more successfully transplanted isologously than those from rats given carcinogen in the diet for 3 months. As might be expected, autologous transplants of well-developed hepatomas appeared earlier and grew more rapidly than the corresponding isologous transplants. All homologous subcutaneous transplants in Sprague-Dawley rats and heterologous intracerebral transplants in Hauschka mice failed to grow within 8 to 12 months.