Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney

被引：0

作者：

Ricarda Thier

Frederike A. Wiebel

Andreas Hinkel

Andreas Burger

Thomas Brüning

Konrad Morgenroth

Theodor Senge

Michael Wilhelm

Thomas G. Schulz

机构：

[1] Institut für Arbeitsphysiologie an der Universität Dortmund,

[2] Ardeystrasse. 67,undefined

[3] D-44139 Dortmund,undefined

[4] Germany,undefined

[5] Urologische Universitätsklinik Marienhospital Herne,undefined

[6] Widumer Strasse 8,undefined

[7] D-44627 Herne,undefined

[8] Germany,undefined

[9] Institut für Allgemeine und Spezielle Pathologie,undefined

[10] Ruhr-Universität Bochum,undefined

[11] Universitätsstrasse 150,undefined

[12] D-44780 Bochum,undefined

[13] Germany,undefined

[14] Institut für Hygiene,undefined

[15] Sozial-und umweltmedizin,undefined

[16] Ruhr-Universität Universitätsstrasse. 150,undefined

[17] 44780 Bochum,undefined

[18] Germany,undefined

[19] Institut für Arbeits- und Sozialmedizin,undefined

[20] Universität Göttingen,undefined

[21] Waldweg 37,undefined

[22] D-37073 Göttingen,undefined

[23] Germany,undefined

来源：

Archives of Toxicology | 1998年 / 72卷

关键词：

Key words Glutathione transferase; GSTT1-1 ; Polymorphism ; Methyl chloride ; Dichloromethane ; 1; 2-Epoxy-3-(p-nitrophenoxy) propane;

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摘要：

Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation␣between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/ rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.

引用

页码：622 / 629

页数：7