Enhanced regional expression of glutathione S-transferase P1-1 with colocalized AP-1 and CYP 1A2 induction in chlorobenzene-induced porphyria.
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.
Thomas
R S
RS
Department of Environmental Health, Colorado State University, Fort Collins 80523-1680, USA.
Gustafson
D L
DL
Ramsdell
H S
HS
el-Masri
H A
HA
Benjamin
S A
SA
Yang
R S
RS
D000818:Animals; D015153:Blotting, Western; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000201:enzymology / Q000473:pathology; D002722:Chlorobenzenes / Q000633:toxicity*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D005456:Fluorescent Dyes; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D011164:Porphyrias / Q000139:chemically induced / Q000201:enzymology*; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*
D002722:Chlorobenzenes; D005456:Fluorescent Dyes; D007527:Isoenzymes; D011166:Porphyrins; D018808:Transcription Factor AP-1; D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase