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Age-dependent Regulation of the Tumorigenic Potential of Neoplastically Transformed Rat Liver Epithelial Cells by the Liver Microenvironment¹

Department of Pathology and Curriculum in Toxicology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

Neoplastically transformed rat liver epithelial cell lines (GN6TF and GP7TB), which form tumors with short latency at s.c. or i.p. transplantation sites of syngeneic rats, did not form tumors or were weakly tumorigenic following transplantation into the livers of young adult rats and expressed increasing tumorigenicity in livers of increasingly aged rats. These results suggest that progressive alterations in the hepatic parenchyma with increasing age enabled tumor formation by providing a less suppressive microenvironment for expression of the tumorigenic phenotype. Age is widely recognized as a significant risk factor in the development of neoplasia; this study describes a model for investigation of the influence of age-dependent changes in the hepatic microenvironment on the development of hepatic cancer.

¹ Supported by NIH Grants CA 29323 and CA 59486 and Training Grant T32 ES 07126 (to K. D. M.). Supported in part by NIH Training Grant T32 ES 07017 (to W. B. C.) and Postdoctoral Fellowship 3867 from the American Cancer Society (to W. B. C.).

² To whom requests for reprints should be addressed.

Received 4/29/94. Accepted 5/26/94.

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