| Cytotoxicity and metabolism of prednimustine, chlorambucil and prednisolone in a Chinese hamster cell line. | |
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MedLine Citation:
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PMID: 3948307 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prednimustine and chlorambucil induce dose- and time-dependent cell death in V79 Chinese hamster cells in vitro. Prednimustine was found to be 3-4 times more potent than either chlorambucil or an equimolar mixture of its components chlorambucil and prednisolone after 24 h treatment. Prednimustine was hydrolyzed to prednisolone and chlorambucil in the system, and the concentration of prednimustine was reduced by one half within 15 h. Prednisolone was not further metabolized, but chlorambucil was rapidly inactivated by dechlorination, the half-life being 2.5 h. No dechlorinated prednimustine was formed during the experiments. The higher stability of prednimustine than chlorambucil is probably due to protective binding to different serum proteins from those that bind chlorambucil. Substitution of fetal calf serum by human serum albumin revealed that hydrolysis of prednimustine is catalyzed by esterases present in the serum. In similar substitution experiments cell survival studies indicated that prednimustine itself was not cytotoxic. Rather, cytotoxicity was found to correlate with hydrolysis to chlorambucil. Thus, it appears that the prolonged availability of chlorambucil is responsible for the increased potency of prednimustine in this system. |
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Authors:
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B Hartley-Asp; P O Gunnarsson; J Liljekvist |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 16 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 1986 |
Date Detail:
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Created Date: 1986-04-02 Completed Date: 1986-04-02 Revised Date: 2005-11-17 |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: GERMANY, WEST |
Other Details:
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Languages: eng Pagination: 85-90 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbon Radioisotopes Cell Line Cell Survival / drug effects* Chlorambucil / analogs & derivatives*, metabolism, toxicity* Chromatography, High Pressure Liquid Cricetinae Cricetulus Electrophoresis, Polyacrylamide Gel Half-Life Humans Hydrolysis Kinetics Male Prednimustine / metabolism, toxicity* Prednisolone / metabolism, toxicity* Time Factors Tritium |
| Chemical | |
Reg. No./Substance:
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0/Carbon Radioisotopes; 10028-17-8/Tritium; 29069-24-7/Prednimustine; 305-03-3/Chlorambucil; 50-24-8/Prednisolone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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