Greater expression of transforming growth factor alpha and proliferating cell nuclear antigen staining in mouse hepatoblastomas than hepatocellular carcinomas induced by a diethylnitrosamine-sodium phenobarbital regimen

Toxicol Pathol. 2001 Jul-Aug;29(4):479-82. doi: 10.1080/01926230152499962.

Abstract

Transforming growth factor alpha (TGF-alpha) is a potent stimulator of normal hepatocyte proliferation, considered to have relationship to the liver regeneration or carcinogenesis. In this study, we investigated immunohistochemically the association between expression of TGF-alpha and cell proliferation activity in mouse hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs) induced in B6C3F1 mice by diethylnitrosamine and sodium phenobarbital. The TGF-alpha-positive rate in HBs (29.2%) was significantly higher than that in HCCs (12.7%). Likewise, the proliferating cell nuclear antigen-positive rate (22.2%) was higher than the HCC value (14.5%). On the individual data for both TGF-alpha and PCNA, most of the HBs showed higher positive rates than HCCs. In HBs, TGF-alpha was localized only in the nuclei, whereas some HCC cells stained positive both in their nuclei and cytoplasm (0.6%). These results suggest expression of TGF-alpha and its localization might be linked to cell proliferation and play a role in malignant progression of mouse HBs.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Carcinogenicity Tests / methods
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Division / physiology
  • Cell Nucleus / chemistry
  • Cell Nucleus / drug effects
  • Cytoplasm / chemistry
  • Cytoplasm / drug effects
  • Diethylnitrosamine / administration & dosage
  • Diethylnitrosamine / pharmacology*
  • Hepatoblastoma / chemically induced
  • Hepatoblastoma / metabolism*
  • Hepatoblastoma / pathology
  • Immunohistochemistry
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / metabolism*
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Phenobarbital / administration & dosage
  • Phenobarbital / pharmacology*
  • Proliferating Cell Nuclear Antigen / analysis*
  • Proliferating Cell Nuclear Antigen / immunology
  • Time Factors
  • Transforming Growth Factor alpha / biosynthesis*
  • Transforming Growth Factor alpha / immunology

Substances

  • Proliferating Cell Nuclear Antigen
  • Transforming Growth Factor alpha
  • Diethylnitrosamine
  • Phenobarbital