title: Preneoplastic liver cell foci expansion induced by thioacetamide toxicity in drug-primed mice.
abstract: Mice primed by feeding griseofulvin or diethyl 1,4-dihydro 1,4,6-trimethyl 3,5-pyridine decarboxylate for 5 months followed by drug withdrawal for 1 month (drug-primed mice) were given thioacetamide intraperitoneally, and the livers were subsequently studied at intervals up to 7 days. The hepatocellular proliferative response was measured by immunostaining for proliferative cell nuclear antigen. Necrosis was followed by measuring ALT. Mallory bodies were identified by immunoperoxidase stains for ubiquitin and cytokeratin. Preneoplastic foci were localized using immunofluorescence stain for glutathione S-transferase (GST mu) and histochemical stain for gamma glutamyl transpeptidase (GGT). The results showed that the preneoplastic foci selectively proliferated and expanded and formed nodules as indicated by quantitation of nuclei stained positive for proliferating cell nuclear antigen after thioacetamide treatment. Data support the hypothesis that the preneoplastic foci consisted of clones of hepatocytes which preferentially express GST mu, GGT and Mallory bodies. These preneoplastic cells selectively proliferate in response to the promoter effects of necrosis-induced liver cell regeneration ("chemical partial hepatectomy").
authors.affiliation: Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90509, USA.
authors.forename: M Waheed
authors.initials: MW
authors.lastname: Roomi
authors.forename: Karl
authors.initials: K
authors.lastname: Gaal
authors.forename: Qi X
authors.initials: QX
authors.lastname: Yuan
authors.forename: Barbara A
authors.initials: BA
authors.lastname: French
authors.forename: Paul
authors.initials: P
authors.lastname: Fu
authors.forename: Fawzia
authors.initials: F
authors.lastname: Bardag-Gorce
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D005982:Glutathione Transferase / Q000032:analysis; D006118:Griseofulvin / Q000008:administration & dosage; D022781:Hepatocytes / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology* / Q000502:physiology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008115:Liver Regeneration; D051379:Mice; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage; D013853:Thioacetamide / Q000633:toxicity*; D005723:gamma-Glutamyltransferase / Q000032:analysis
chemical_list: D011725:Pyridines; C513554:diethyl 1,4-dihydro-1,4,6-trimethyl-3,5-pyridinedicarboxylate; D013853:Thioacetamide; D006118:Griseofulvin; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase