Enhanced regional expression of glutathione S-transferase P1-1 with colocalized AP-1 and CYP 1A2 induction in chlorobenzene-induced porphyria

• Published in: Toxicology and applied pharmacology Vol. 150; no. 1; pp. 22 - 31
• Main Authors: THOMAS, R. S, GUSTAFSON, D. L, RAMSDELL, H. S, EL-MASRI, H. A, BENJAMIN, S. A, YANG, R. S. H
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 01.05.1998
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Chemical and Drug Induced Liver Injury, Chronic - enzymology; Chemical and Drug Induced Liver Injury, Chronic - pathology; Chemical and industrial products toxicology. Toxic occupational diseases; Chlorobenzenes - toxicity; Cytochrome P-450 CYP1A2 - biosynthesis; Fluorescent Dyes; Glutathione Transferase - biosynthesis; Immunohistochemistry; Isoenzymes - biosynthesis; Liver - enzymology; Liver - pathology; Male; Medical sciences; Microscopy, Fluorescence; Porphyrias - chemically induced; Porphyrias - enzymology; Porphyrins - metabolism; Rats; Rats, Inbred F344; Toxicology; Transcription Factor AP-1 - biosynthesis; Various organic compounds; Porphyria; Photosensitivity; Skin disease; Late; Premalignant lesion; Rat; Enzyme; Isozyme; Toxicity; Transferases; Cytochrome P450; Rodentia; Biological marker; Metabolic diseases; Hepatic disease; Gene expression; Enzymopathy; Vertebrata; Mammalia; Glutathione transferase; Animal; Pigments; Skin
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1998.8385

A distinct, nonfocal expression pattern was observed for glutathione S-transferase P1-1 (rGSTP1-1) in rats exposed to either hexachloro-(HCB) or pentachlorobenzene (PeCB). The nonfocal expression was localized to the centrilobular region with the most intense staining nearest the central vein. A Western blot analysis revealed a 5- and 15-fold induction of rGSTP1-1 with PeCB and HCB treatment on an equal molar basis, respectively. Evaluation of porphyrin fluorescence also revealed a centrilobular accumulation with average porphyrin measurements of 0.319, 0.590, and 0.206 micrograms/g tissue for PeCB, HCB, and corn-oil controls, respectively. Due to the role of Activator Protein-1 (AP-1) in rGSTP1-1 expression and CYP 1A2 in the pathogenesis of porphyria cutanea tarda, immunohistochemical localization of c-jun, c-fos, and CYP 1A2 was also performed. Increased expression and colocalization within the liver lobule was observed for c-jun, c-fos, CYP 1A2, rGSTP1-1, and areas of porphyrin accumulation. These observations are consistent with studies that have associated the induction of GST-P with jun- and fos-related gene products.