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Archives of Toxicology

, Volume 75, Issue 10, pp 618–624 | Cite as

Glutathione S-transferase Pi expression in forestomach carcinogenesis process induced by gavage-administered 2,4-hexadienal in the F344 rat

  • Abraham Nyska
  • Cindy R. Moomaw
  • Liat Lomnitski
  • Po Chan
Genotoxicity

Abstract.

2,4-Hexadienal (2,4-Hx), an unsaturated aldehyde formed by in vivo and in vitro peroxidation of unsaturated lipid induced, in National Toxicology Program (NTP) gavage studies of F344 rats, forestomach hyperplasia in 13-week and 2-year exposures and squamous papilloma and carcinoma in 2-year studies. Hyperplasia was characterized by thickening of all layers of epithelium with particularly prominent proliferation of the basal cells. The present investigation describes the nature and potential significance of glutathione-S-transferase-Pi (GST-Pi) immunoexpression of normal forestomach epithelium, compared to that of 2,4-Hx-related basal cell hyperplasia and squamous cell papilloma and carcinoma. Paraffin-embedded forestomachs from these NTP studies were used to investigate possible correlations between the carcinogenic process and expression of GST-Pi, a physiological metabolic barrier and an inducible phase II detoxifying enzyme suggested to decrease the responsiveness of reactive oxygen species (ROS) and organic electrophilic compounds. The amount of immunopositive staining was graded on a scale of 0 (no staining) to 4 (marked staining). The simple basal epithelium of control rats showed strong immunopositivity. In cases of basal cell hyperplasia from the 13-week and 2-year studies, these cells usually expressed strong immunopositivity for GST-Pi (grade 3 to 4). In the 2-year treated animals only, occasional focal reduction (grade 0 to 2) in immunoreactivity for GST-Pi was noted. In papillomas and squamous cell carcinomas, a wide range of GST-Pi expression was observed, perhaps indicating irregularities in its induction or change in the phenotype of these cells compared to normal or hyperplastic ones. Reduced expression of GST-Pi by the foci of basal cell hyperplasia and in tumor cells may suggest changes in cellular protection from oxidative or electrophilic DNA damage; these changes may result in genetic alterations and be the precursor to clonal expansion.

Basal cell hyperplasia F344 rat Glutathione-S-transferase-Pi 2,4-Hexadienal Stomach 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Abraham Nyska
    • 1
  • Cindy R. Moomaw
    • 1
  • Liat Lomnitski
    • 2
  • Po Chan
    • 3
  1. 1.Laboratory of Experimental Pathology, MD B3–06, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, PO Box 12233, Research Triangle Park, North Carolina 27709, USA
  2. 2.Institute of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel
  3. 3.Environmental Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, North Carolina 27709, USA

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