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.
Cameron
R G
RG
Department of Pathology, University of Toronto, Ontario, Canada.
D015073:2-Acetylaminofluorene / Q000627:therapeutic use; D000818:Animals; D001564:Benzo(a)pyrene; D014408:Biomarkers, Tumor / Q000032:analysis*; D001973:Bromodeoxyuridine / Q000032:analysis; D002455:Cell Division; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005982:Glutathione Transferase / Q000032:analysis; D006498:Hepatectomy / Q000379:methods; D007124:Immunoenzyme Techniques; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D008115:Liver Regeneration; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy; D051381:Rats; D011916:Rats, Inbred F344
D014408:Biomarkers, Tumor; D001564:Benzo(a)pyrene; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase; D001973:Bromodeoxyuridine