Identification of the putative first cellular step of chemical hepatocarcinogenesis.

A first cellular step of chemical hepatocarcinogenesis is characterized by identifying hepatocytes with preneoplastic properties: positivity for glutathione transferase-P or GST-P+, cell proliferation marked by bromodeoxyuridine or BUDR+, resistance to hepatotoxins and persistence. Hepatocellular doublets, both GST-P+ and BUDR+, are located immunohistochemically 4 days after a single dose of diethylnitrosamine, 25 mg/kg, using antibodies bound to different chromogens. GST-P+ hepatocytes proliferate after selection for resistance to 2-acetylaminofluorene, and persist in the absence of selection for 6 weeks. The actual probability of the same cell being GST-P+ and BUDR+ is 200 times the expected value implying close links between cell proliferation and GST-P expression at initiation.