Production of Transplantable Hepatomas by Intrasplenic Implantation of Normal Liver in the Mouse

Summary

Intrasplenic implantation of liver tissue was carried out in an inbred strain of mice in which spontaneous hepatomas have not been found. The donors were 13-, 14-, and 18-day fetuses and 1-, 7-, and 90-day-old normal mice; also implanted was liver containing hyperplastic nodules from donors that had received 11, 18, 24, and 48 administrations of carbon tetrachloride; regenerating liver, 48 hours after partial hepatectomy; and cholangiole-laden liver from a choline-deficient mouse. Parenchymal liver cells of fetal, 1-, and 7-day-old mice increased in size, differentiated to resemble adult hepatic cells, and persisted in the host's spleen up to 20 months after implantation, without conspicuous proliferation. Implanted adult liver parenchyma persisted in the spleen in only 1 of 47 hosts examined after 10 to 21 months. Duct cells survived more than 10 months in the spleens of only those hosts that received implants of liver containing large numbers of proliferating cholangioles. The 7-day-old liver and all types of adult liver, but not livers from fetuses and 1-day-old mice, apparently gave rise to a small number of intrahepatic nodules that subsequently were serially transplantable in the spleen and, later, subcutaneously. Six were hepatomas and one was a reticulum-cell sarcoma. We propose that these neoplasms arose from hepatic tissue implanted in the spleen and then forced into or migrated into the host's liver by way of the portal vein.