Detection of serum and intrahepatic hepatocyte growth factor during DEN-induced carcinogenesis in the rat

We studied changes in serum levels of hepatocytes growth factor (HGF), as well as the levels of HGF expression in the livers, of rats with chemically-induced cancer. Rats were given diethylnitrosamine (DEN) orally in their drinking water. The serum HGF level was measured by enzyme-linked immunosorbent assay. The degree of HGF expression in liver, detected by immunoperoxidase staining, was classified from negative to high. For two DEN-treated rats, the nucleotide sequence of HGF DNA was determined from the livers containing cancerous foci (CA). The serum HGF levels tended to be higher in the DEN-treated rats than in the control rats. In the DEN-treated rats, low to moderate levels of expression of HGF were found in hepatocytes with strong atypia at 8, 12, and 14 weeks. Low levels of HGF expression were found in moderately differentiated cancer cells. The sequence of HGF showed the loss of three nucleotides, in comparison with a sequence reported previously. In conclusion, the results of this study suggest that HGF may contribute to hepatocarcinogenesis in chemically induced cancer in rats.