Metabolism of cyclophosphamide by purified cytochrome P-450 from microsomes of phenobarbital-treated rats
| Autor: | Surendra K. Bansal, A.J. Marinello, J. Love, R.F. Struck, Hira L. Gurtoo, P. Kari, J. Kalin, J.A. Montgomery |
|---|---|
| Rok vydání: | 1984 |
| Předmět: |
Chemical Phenomena
Cytochrome Metabolite Sulfur Oxides Biophysics Pharmacology Tritium Biochemistry chemistry.chemical_compound Cytochrome P-450 Enzyme System medicine Animals heterocyclic compounds Carbon Radioisotopes Cyclophosphamide Molecular Biology Thionyl biology Diazomethane Cell Biology Metabolism Rats Chemistry chemistry Phenobarbital Toxicity Microsomes Liver cardiovascular system biology.protein Microsome Chlorine medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 120:390-396 |
| ISSN: | 0006-291X |
| Popis: | Incubation of [ 3 H]-sidechain-labeled and [ 14 C]-C(4)-ring-labeled cyclophosphamide (CPA) with purified cytochrome P-450 from liver microsomes of rats treated with phenobarbital resulted in the production of a major metabolite that contained both labels, was unaffected by diazomethane, possessed high polarity, was identical in TLC and HPLC behavior to a synthetic standard, didechlorodihydroxy-CPA, and was converted to CPA and bis(2-chloroethyl)amine by thionyl choloride. These results indicate that phenobarbital-inducible cytochrome P-450 is able to dechlorinate CPA and may account, in part, for the inability of phenobarbital to enhance the therapeutic activity and toxicity of this important anticancer and immunosuppressive agent. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|