Lipid peroxidation end products-responded induction of a preneoplastic marker enzyme glutathione S-transferase P-form (GST-P) in rat liver on admistration via the portal vein

Mutat Res. 2001 Nov 1;483(1-2):65-72. doi: 10.1016/s0027-5107(01)00225-1.

Abstract

The in vivo induction mechanism of a preneoplastic marker enzyme, glutathione S-transferase P-form (GST-P), by a number of carcinogens and some noncarcinogens such as anti-oxidants [Proc. Natl. Acad. Sci. U.S.A. 85 (1984) 3964] has remained to be solved. Among the various administration routes tested, GST-P became immunohistochemically demonstrable in the liver centrilobular zone 3 after 24-48h on administration of prostaglandin J2's, 15-deoxy-Delta(12,14)-PGJ2, PGJ2 and Delta(12)-PGJ2 to male rats via the portal vein, whereby the animals had been pretreated with Soya oil intraperitoneally to exhaust fatty acid binding proteins. Unsaturated aldehydes, 4-hydroxynonenal, crotonaldehyde and acrolein, given by the same route induced putatively preneoplastic single cells positive for GST-P. As these lipid peroxidation end products are the substrates as well as inducers of the enzyme, its physiological function could be their detoxication. These results indicate that GST-P expression can be mediated through lipid peroxidation possibly accounting for induction observed with a wide variety of carcinogens. In addition, present method may also be of use as a direct, simple, rapid, and sensitive in vivo test in examination of other biological responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / biosynthesis*
  • Carcinogenicity Tests / methods
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity*
  • Carrier Proteins / metabolism
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Glutathione Transferase / biosynthesis*
  • Injections, Intravenous
  • Lipid Peroxidation* / drug effects
  • Liver / drug effects*
  • Liver / metabolism*
  • Liver Neoplasms, Experimental / metabolism
  • Male
  • Neoplasm Proteins*
  • Nerve Tissue Proteins*
  • Portal Vein
  • Precancerous Conditions / metabolism
  • Prostaglandin D2 / administration & dosage
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Soybean Oil / administration & dosage

Substances

  • Biomarkers, Tumor
  • Carcinogens
  • Carrier Proteins
  • Fabp7 protein, rat
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • 9-deoxy-delta-9-prostaglandin D2
  • Soybean Oil
  • Glutathione Transferase
  • Prostaglandin D2