| Modulation of cytarabine metabolism in the human promyelocytic leukemia cell line HL-60 by polyhydroxy-substituted benzohydroxamic acids. | |
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MedLine Citation:
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PMID: 6957264 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Two potent new ribonucleotide reductase inhibitors, 3,4,5-trihydroxybenzohydroxamic acid (VF 122) and 3,4-dihydroxybenzohydroxamic acid (VF 147), were investigated for their ability to modulate the cellular pharmacology of cytarabine (ara-C) in HL-60 cells. VF 122 and VF 147 increased the total cellular uptake of ara-C by a mean (+/- SE) of 8% +/- 3% and 29% +/- 3%, respectively, when measured 2 hours after the start of exposure to 0.1 microM ara-C. This effect was evident after only 10 minutes of exposure to the riboNucleotide reductase inhibitor and did not vary significantly over the concentration range of 10-100 microM for either agent. VF 122 enhanced the incorporation of ara-CTP into DNA by 3.6-fold; VF 147 produced a 5.6-fold increase. In comparison, the maximum enhancement achievable with hydroxyurea was 2.1-fold, and with thymidine was 1.8-fold. These results provide a biochemical rationale for further investigation of these agents in combination with ara-C. |
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Authors:
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S B Howell; S Gill; H L Elford |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer treatment reports Volume: 66 ISSN: 0361-5960 ISO Abbreviation: Cancer Treat Rep Publication Date: 1982 Oct |
Date Detail:
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Created Date: 1982-12-16 Completed Date: 1982-12-16 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7607107 Medline TA: Cancer Treat Rep Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1825-9 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Cytarabine / metabolism* DNA / metabolism Humans Hydroxamic Acids / pharmacology* Leukemia, Myeloid / metabolism* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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CA-25336/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hydroxamic Acids; 147-94-4/Cytarabine; 69839-82-3/3,4,5-trihydroxybenzohydroxamic acid; 69839-83-4/3,4-dihydroxybenzohydroxamic acid; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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