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Progression in Hepatocarcinogenesis: Differences in Growth and Behavior of Transplants of Early and Later Hepatocyte Nodules in the Rat Spleen¹

Departments of Pathology of the University of Toronto [M. T., G. L., M. A. H. and E. F.], Toronto, Ontario, Canada M5S 1A8, and of the University of Guelph [M. A. H.], Guelph, Ontario, Canada

Hepatocyte nodules were induced in Fischer 344 rats using the resistant hepatocyte model. Nodules harvested at 5, 24, or 25 weeks after initiation were isolated, diced, and transplanted into the spleen of normal rats and observed for periods up to 104 weeks. In the first experiment, 50% of the animals developed hepatocellular carcinoma, some with invasion and metastasis, by 70 to 104 weeks. In the second experiment, transplants of 5-week nodules grew very slowly and diffusely in the spleen, as did normal liver, but retained at least some of their phenotypic properties. In contrast, transplants of 25-week nodules grew into nodules up to 2.5 cm in diameter by 70 weeks. Two of the larger nodules had smaller nodules within resembling trabecular carcinoma. Transplants from the liver surrounding the 25-week nodules did not grow and produced no nodules by 70 weeks after transplantation. The implications of these observations in the study of progression in hepatocarcinogenesis are discussed briefly.

¹ Supported by grants from the National Cancer Institute of Canada, the Medical Research Council of Canada (MT-5994), and the USPHS (CA 21157 from the National Cancer Institute). A preliminary report of some of this research was presented at the Annual Meeting of the American Association for Cancer Research, May 1983 (28).

² To whom requests for reprints should be addressed, at Department of Pathology, Medical Sciences Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

Received 3/ 3/87. Revised 6/ 4/87. Accepted 6/ 5/87.