Response of Hepatocytes Transplanted into Syngeneic Hosts and Heterotransplanted into Athymic Nude Mice to Peroxisome Proliferators

Janardan K. Reddy, Randy L. Jirtle, Thomas K. Watanabe, Neerad K. Reddy, George Michalopoulos, Saeed A. Qureshi

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The development of a transplantation system by which rat hepatocytes can be implanted and remain viable in the dorsal fascia of two-thirds hepatectomized syngeneic hosts provides an opportunity to examine whether such transplanted hepatocytes retain the capacity to recognize and respond to the peroxisome proliferators 2-[4-(2,2-dichtorocydopropyl)phenoxy]-2-methylpropionic add (ciprofibrate), a hypolipidemic drug, and di-(2-ethyihexyl)phthalate (DEHP), an industrial plastidzer. Male F344 rats with transplanted rat hepatocytes were fed a control diet or a diet containing either 0.05% dprofibrate (w/w) or 2% DEHP (v/w). After 4 weeks, the animals were sacrificed, and transplanted hepatocytes as well as pieces of homotopic (host) rat liver were processed for electron microscopy and for the cytochemical localization of catatase. Morphometric analysis of transplanted hepatocytes revealed a significant increase in the numerical density of peroxisomes in both dprofibrate- and DEHP-fed rats. The volume density of peroxisomes in transplanted hepatocytes increased 9.2- and 5.3-fold, respectively, in dprofibrate- and DEHP-fed rats, whereas the volume density of mitochondria remained essentially unchanged. The magnitude of increase in peroxisome volume density in transplanted hepatocytes was comparable to increases in the volume density of these organelles in the liver parenchymal cells of syngeneic hosts. The present study also demonstrates that hepatocytes isolated from cat liver and heterotransplanted into partially hepatectomized athymic nude mice retain their biological integrity and respond to the peroxisome proliferative effect of dprofibrate. This observation suggests the possibility that hepatocytes obtained from small segments of liver of humans, primates, and other species and heterotransplanted into nude mice might provide a valuable model system for toxicological evaluation of chemicals. These studies suggest that hepatocytes, irrespective of their location in the body, recognize the peroxisome proliferator or its active metabolites), which stimulates the expression of peroxisome-specific genes in these cells.

Original languageEnglish (US)
Pages (from-to)2582-2589
Number of pages8
JournalCancer Research
Volume44
Issue number6
StatePublished - Jun 1 1984

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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