| Autor: |
VANBEERENDONK, GJM, PEARSON, PG, MEIJER, DKF, NELSON, SD, MEERMAN, JHN |
| Jazyk: |
angličtina |
| Rok vydání: |
1995 |
| Předmět: |
|
| Zdroj: |
Fundamental and applied toxicology, 28(1), 111-117 |
| ISSN: |
0272-0590 |
| Popis: |
The metabolism of tris(2,3-dibromopropyl) phosphate (Tris-BP) was compared with that of completely deuterated Tris-BP (D15-Tris-BP) in an isolated, recirculating rat liver perfusion system in order to determine the relative quantitative importance of two different biotransformation pathways of Tris-BP: (i) cytochrome P450-mediated metabolism and (ii) GSH S-transferase-mediated metabolism. To accomplish this we quantitated the biliary excretion of S-(3-hydroxypropyl)glutathione (GSOH) as a marker metabolite for cytochrome P450-mediated metabolism and that of S-(2,3-dihydroxypropyl) glutathione (GSOHOH) as a marker metabolite for GSH S-transferase-mediated metabolism. Complete deuterium substitution of Tris-BP significantly decreased the formation of GSOH, whereas there was no effect on the formation of GSOHOH. Because our previous studies showed a large decrease in genotoxicity of D15-Tris-BP compared to Tris-BP, the present results support our hypothesis that cytochrome P450-mediated metabolism is responsible for the genotoxic effects of Tris-BP in the rat liver. (C) 1995 Society of Toxicology |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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