Ciprofibrate and triiodothyronine do not suppress in vivo induction of placental glutathione S-transferase expression in rat hepatocytes

• Published in: Cancer letters Vol. 151; no. 2; pp. 153 - 159
• Main Authors: Ledda-Columbano, Giovanna M, Pibiri, Monica, Perra, Andrea, Piga, Rosaria, Loi, Roberto, Dore, Maria, Shinozuka, Hisashi, Columbano, Amedeo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 14.04.2000; Elsevier
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Clofibric Acid - analogs & derivatives; Clofibric Acid - pharmacology; Enzyme Induction - drug effects; Fibric Acids; Glutathione S-transferase P; Glutathione Transferase - biosynthesis; Glutathione Transferase - genetics; Immunohistochemistry; Lead - pharmacology; Lead nitrate; Liver - cytology; Liver - drug effects; Liver - enzymology; Liver carcinogenesis; Male; Medical sciences; Nitrates - pharmacology; Peroxisome proliferators; Peroxisome Proliferators - pharmacology; Placenta - enzymology; Rats; Rats, Wistar; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Triiodothyronine; Triiodothyronine - pharmacology; Tumors; Peroxisome proliferators; Triiodothyronine; Lead nitrate; Liver carcinogenesis; Glutathione S-transferase P; Immunohistochemistry; Rat; Enzyme; Fibrate derivatives; Transferases; Rodentia; Hepatic disease; Anticarcinogen; Gene expression; Lead Nitrates; Carcinogenesis; Peroxisome proliferator; Carcinogen; Vertebrata; Mammalia; Ciprofibrate; Hepatocyte; Glutathione transferase; Animal; Immunoblotting assay; Digestive diseases
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(99)00407-3

Studies on hepatocyte primary cultures have suggested that loss of expression of the placental form of glutathione S-transferase in peroxisome proliferator (PP)-induced hepatocarcinogenesis is due to inhibition of glutathione S-transferase P (GSTP) transcription by the PPs. In the present study, we have analyzed the effect of a PP, ciprofibrate, and of another ligand of nuclear receptors, 3,3′,5-triiodo- l-thyronine (T3), on GSTP mRNA and protein levels in an in vivo model where GSTP expression was induced in Wistar rats by pre-treatment with a single dose of lead nitrate. Results indicate that administration of ciprofibrate or T3, immediately after lead nitrate treatment, did not exert any inhibitory effect on GSTP mRNA and protein levels, as revealed by both Western and immunohistochemical analysis. The results indicate that PPs do not inhibit hepatocyte GSTP expression induced in vivo by lead nitrate and suggest that inhibition of GSTP expression by PPs may not necessarily be the cause for the rapid disappearance of GSTP-positive preneoplastic lesions observed after a short term exposure to these agents.