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Titolo:
MOBILIZATION OF PENTACHLOROPHENOL BY GLUTATHIONE-S-TRANSFERASE-MU INCREASES CELLULAR TOXICITY
Autore:
BAIN LJ; LEBLANC GA;
Indirizzi:
N CAROLINA STATE UNIV,DEPT TOXICOL,BOX 7633 RALEIGH NC 27695
Titolo Testata:
Pesticide biochemistry and physiology
fascicolo: 1, volume: 54, anno: 1996,
pagine: 65 - 72
SICI:
0048-3575(1996)54:1<65:MOPBGI>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
LUNG-CANCER; RAT-LIVER; BINDING; EXPRESSION; PROTEIN; SUSCEPTIBILITY; POPULATION; INHIBITION; URINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
L.J. Bain e G.A. Leblanc, "MOBILIZATION OF PENTACHLOROPHENOL BY GLUTATHIONE-S-TRANSFERASE-MU INCREASES CELLULAR TOXICITY", Pesticide biochemistry and physiology, 54(1), 1996, pp. 65-72

Abstract

Glutathione S-transferases (GSTs) are a class of proteins that have intracellular binding and sequestration, as well as catalytic, capabilities. This study investigated the role of GSTs in the intracellular mobilization of pentachlorophenol (PCP). A single mouse GST isoform, GSTmu, specifically and competitively bound PCP with a k(i) = 7 mu M with respect to the substrate 1-chloro-2,4-dinitrobenzene (CDNB), yet didnot metabolize PCP. Instead, the binding of GST mu to PCP resulted inthe partitioning of PCP from lipid to aqueous compartments. The physiological significance of the mobilization was then investigated using two mouse hepatocyte cell lines that differ significantly in their expression of GST mu. These cells were treated with butylated hydroxyanisole (BHA) to induce GST mu and provided several levels of GST mu expression. The toxicity of PCP to these cells based on trypan blue dye exclusion was assessed, which demonstrated a significant correlation between GST mu levels within the cell and PCP toxicity. The BHA-treated,high GST mu expressor cells were approximately 40% more sensitive to PCPtoxicity than were the untreated low GST mu expressors, suggesting that GST mu was acting to make PCP more bioavailable toxicity toxicity. Furthermore, the increase in toxicity was not due to a difference in PCP accumulation or in GST metabolism by the cells. These results suggest that GST mu may increase the cellular toxicity of PCP by mobilizingthis lipophilic compound within the cell. (C) 1996 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/08/20 alle ore 06:52:41