Abstract

BACKGROUND
N-nitrosomorpholine (NNM) is a genotoxic hepatocarcinogenic agent. Preneoplastic and neoplastic hepatocyte lesions were induced in rats by oral exposure to NNM (200 mg/L) in a stop model experiment. Platelet-derived growth factor receptor (PDGF-R) is a tyrosine kinase receptor that works with PDGF, stimulating cellular growth and proliferation. The present study was designed to determine the role of PDGF-R alpha expression in hepatocellular neoplasms and precursors.
METHODS
Seventeen rats out of a starting number of 30 died. From the fifth week until the 24th week one or two rats were evaluated. Preneoplastic single cells or foci, foci of altered hepatocytes (FAH) hepatocellular adenomas (HCA) and hepatocellular carcinomas (HCC) were studied histologically, and the expressions of GSTp and PDGF-R alpha by immunohistochemistry.
RESULTS
At the fifth week, GSTp +single cells showed PDGF-R alpha expression (20.8+/-5.8%). At the sixth week, GSTp +single cells, located at periportal areas, co-expressed PDGF-R alpha (43.4+/-9.6%). Over the next several weeks periportal hepatocytes showed weaker PDGF-R alpha expression but no GSTp. GSTp+FAH, and all HCA, demonstrated no PDGF-R alpha expression. However, nine out of 10 (90%) HCC showed PDGF-R alpha expression.
CONCLUSIONS
These data showed that there were two peaks of PDGF-R alpha expression, and suggest that the earlier expression is related with the response to NNM-induced hepatocyte toxicity, and that the later response is associated to malignant transformation.

• Keywords: N-nitrosomorpholine;Rat liver;PDGF receptor;Malignant transformation;