Short-term diethylnitrosamine-induced oval cell responses in three strains of mice

The oval cells of the liver have been identified as target cells of chemical carcinogens during rat hepatocarcinogenesis and are believed to act as liver stem cells. In this study mice (strains C3H/EJ (C3H), C57/BL6J (C57) and hybrid B6C3F1 (F1)) were sacrificed at 1, 3 and 7 days after administration of a single dose of the carcinogen diethylnitrosamine (DEN), and histopathological studies of oval cells were evaluated using Haematoxylin and Eosin (H&E), Picro-Mallory (P-M), alpha-fetoprotein (A-FP) and glutathione S-transferase placental form (GST-pi) staining techniques and electron microscopy (EM). Increased oval cell proliferation was observed as soon as one day following exposure of the mice to DEN, in a manner consistent with C3H and C57 mice exhibiting high and low susceptibility to DEN respectively, with hybrid F1 mice being intermediate in DEN sensitivity. This analysis indicates that, in mice, oval cells are target cells at very early stages of liver carcinogenesis and supports the notion that oval cells are potential liver stem cells.