| Cell kill kinetics of an antineoplastic nucleoside, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine. | |
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MedLine Citation:
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PMID: 8937436 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cytotoxic properties of 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytosine (DMDC) were compared with those of 1-beta-D-arabinofuranosylcytosine (ara-C), using SK-MEL-28(P-36) human melanoma cells. DMDC and ara-C were most cytotoxic to cells in the S phase of the cell cycle. Cell cycle progression in S phase was blocked by both compounds. Treatment with DMDC (1 microgram/mL) or ara-C (1 and 30 micrograms/mL) did not increase cytotoxicity against asynchronous cells when the exposure time was prolonged from 1 to 6 hr, but did increase cytotoxicity thereafter. These findings suggest that cells in S phase are rapidly killed by the treatment but are temporarily prevented or delayed entry into the drug-sensitive S phase. On the other hand, DMDC treatment at a higher concentration (30 micrograms/mL) increased cytotoxicity in a time-dependent manner. Intracellular DMDC 5'-triphosphate (DMDCTP) increased in proportion to exogenous DMDC concentration, which was not saturated by treatment with a maximum concentration of the compound at 80 micrograms/mL. In contrast, intracellular ara-C 5'-triphosphate reached peak level when the cells were treated with ara-C at 8 micrograms/mL. The cytotoxicity of DMDC treatment for 4 hr increased relative to the intracellular DMDCTP accumulated during the period. These findings suggest that in cells treated with DMDC at a high concentration, an effective DMDCTP level is maintained for an extended period after washing out the compound from the medium. Consequently, the cells would be killed in the same way as in the case of extended exposures over 6 hr to DMDC at low concentration or to ara-C, in addition to acute S-phase-specific cytotoxicity. |
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Authors:
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T Ono; A Fujii; K Yamagami; M Hosoya; T Okumoto; S Sakata; A Matsuda; T Sasaki |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical pharmacology Volume: 52 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1996 Oct |
Date Detail:
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Created Date: 1997-01-02 Completed Date: 1997-01-02 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1279-85 Citation Subset: IM |
Affiliation:
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Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Saitama, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
/
metabolism,
pharmacology* Cell Cycle / drug effects Cell Death / drug effects* Cytarabine / pharmacology Deoxycytidine / analogs & derivatives*, metabolism, pharmacology Deoxycytosine Nucleotides / metabolism Humans Kinetics Phosphorylation S Phase / drug effects Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/1-(2-deoxy-2-methylene-erthyro-pentofuranosyl)cytosine 5'-triphosphate; 0/Antineoplastic Agents; 0/Deoxycytosine Nucleotides; 119804-96-5/2'-methyl-2'-deoxyidenecytidine; 147-94-4/Cytarabine; 951-77-9/Deoxycytidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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