Tannic Acid-induced Nucleolar Changes in Hepatocytes Transplanted into Syngeneic or Xenogeneic Host and in Hepatocytes Maintained in Primary Culture

Abstract In this study we have investigated the effect of a single dose of tannic acid, administered s.c., on the nucleolar ultrastructure of hepatocytes transplanted into a syngeneic or xenogeneic host in order to evaluate the validity of our hepatocyte transplantation system as an in vivo alternative to the use of whole animals to test for species and strain differences to the effects of hepatotoxins. Within 4–6 h following tannic acid injection, rat hepatocytes transplanted into the anterior chamber of eye and inguinal fat pads of rat and athymic nude mouse, showed changes of nucleolar components, with separation of ribonucleoprotein containing granules into discrete dark zones. These dark areas were surrounded by light areas consisting of granular and fibrillar components of the nucleolus. These changes were identical to tannic acid-induced nucleolar alterations in the homotopic liver. Hamster and rat hepatocytes xenotransplanted into athymic nude mice also displayed prominent nucleolar alterations in response to tannic acid. The similarity and extent of nucleolar alterations observed in transplanted hepatocytes and the in situ homotopic liver cells attest to the usefulness of the hepatocyte transplantation system for the evaluation of species differences in biological response to toxic/carcinogenic effects of xenobiotics.