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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Metabolism of 1-phthalidyl 5-fluorouracil in rat liver and enzyme induction by phenobarbital.

1. When 1-phthalidyl 5-fluorouracil (PH-FU) was incubated with isolated rat hepatocytes, 5-fluorouracil, 2-carboxybenzaldehyde (CBA) and alpha-hydroxymethylbenzoic acid (HMB) were detected as the major metabolites. 2. The enzymes involved in the metabolism of PH-FU, PH-FU hydrolase and CBA reductase are cytosolic and were induced by treating the rats with phenobarbital (PB). Treatment of rats with 3-methylcholanthrene (3-MC) did not affect either enzyme activity. 3. The PB-induced PH-FU hydrolase was inhibited by NADH and several aldehydes, while NAD stimulated the hydrolase and protected it from inactivation by SH reagents. 4. Study in vivo revealed that treatment of rats with PB accelerated the metabolism of PH-FU in the liver and markedly decreased the blood PH-FU after its oral administration to rats, which resulted in reduction of the anti-tumour activity of PH-FU. This activity was not affected by treatment of the rats with 3-MC.[1]

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