SPARSE DISTRIBUTION OF HEPATOCYTE-GROWTH-FACTOR-PRODUCING CELLS INSIDE HEPATOCELLULAR FOCI IN RATS TREATED WITH HEPATOCARCINOGENS

The distribution of hepatocyte growth factor (HGF)-synthesizing cells in rat liver during development of glutathione S-transferase P form (G ST-P)-positive nodules after diethylnitrosamine initiation followed by promotion with 2-acetylaminofluorene plus partial hepatectomy (PH) wa s investigated using in situ hybridization. HGF-producing cells were n on-parenchymal in nature, and were suspected to be mainly of Kupffer t ype. They were mostly located outside GST-P-positive lesions, in the s urrounding parenchyma. In the oval cell proliferation phase 1 week aft er PH, they increased and they were mainly localized around the portal triads. It is concluded that HGF is directly involved in an endogenou s paracrine growth pathway controlling proliferation in oval cells and in normal, but not GST-P-positive, hepatocytes.