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Redifferentiation as a Basis for Remodeling of Carcinogen-induced Hepatocyte Nodules to Normal Appearing Liver¹

Department of Pathology, Banting Institute, University of Toronto, Toronto, Ontario, Canada M5G 1L5

A system is described for the detailed study of the remodeling of hepatic nodules that appear regularly during liver carcinogenesis with chemicals. With the use of the resistant hepatocyte model and by focusing on the caudate lobe, it has been possible to label with [³H]thymidine all the hepatocytes in hepatocyte nodules without any significant degree of labeling of the surrounding hepatocytes. Through such a model, the persistence of the label, in relation to the organization and appearance of the hepatocytes in the nodules, has been followed for 26 weeks. Nodules do not "disappear" to any significant degree by regression or by replacement with hepatocytes from the surrounding liver. Rather, nodule hepatocytes undergo differentiation to an adult liver phenotype. Thus, differentiation ("redifferentiation") of a carcinogen-induced altered hepatocyte population is seen regularly during carcinogenesis despite the irreversible nature of some of the changes induced by a chemical carcinogen during initiation.

¹ This research was supported by grants from the National Cancer Institute of Canada, the Medical Research Council of Canada (MT-5994), and the National Cancer Institute, NIH (CA-21157). A preliminary report of some of this research was presented at the Annual Meeting of the American Association for Cancer Research, April 1982 (39).

² Present address: First Department of Pathology, Nagoya City University Medical School, Kawasumi, Mizuho-ku, Nagoya 467, Japan.

³ Present address: Department of Pathology, School of Medicine, Yamaguchi University, 1144 Kogushi Ube-City, Yamaguchi-ken, Japan.

⁴ To whom requests for reprints should be addressed, at Department of Pathology, University of Toronto, Banting Institute, 100 College Street, Toronto, Ontario M5G 1L5, Canada.

Received 5/17/83. Accepted 8/ 1/83.

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