| Cell cycle control processes determine cytostasis or cytotoxicity in thymineless death of colon cancer cells. | |
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MedLine Citation:
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PMID: 8069864 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thymidylate synthase (TS) is a target of critical importance to the survival of human colon cancer cells since, upon inhibition, cells subsequently undergo thymineless death induced by dTTP deficiency. Using genetically marked mutants deficient in TS (TS-) and a derived population (Thy4) that is resistant to commitment to thymineless death, resistance was conferred by the ability of cells to arrest at a point either in late G1 or at the onset of S induced by dThd deprivation. Thus, Thy4 cells initially synchronized in G0 by leucine deprivation and released in the absence of dThd remained viable at 5 days, demonstrated delayed onset of nucleosomal ladder formation, and retained clonogenic potential (cytostatic response). In contrast, TS- and asynchronous Thy4 cells lost 50% clonogenic potential in 65 h and > 90% in 5 days (cytotoxic response). [3H]DNA precursor studies indicated failure of synchronized Thy4 but not TS- cells to progress through S, with arrest of Thy4 close to the G1/S boundary. Cell cycle control processes including: (a) the locus of dThd deprivation in G1; and (b) a potential checkpoint close to the G1/S border, may dictate whether consequences of dThd or dTTP restriction become cytostatic or cytotoxic. |
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Authors:
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J A Houghton; F G Harwood; P J Houghton |
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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 research Volume: 54 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1994 Sep |
Date Detail:
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Created Date: 1994-09-27 Completed Date: 1994-09-27 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4967-73 Citation Subset: IM |
Affiliation:
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Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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enzymology,
pathology* Apoptosis / physiology* Cell Cycle Cell Survival Colonic Neoplasms / enzymology, pathology* G0 Phase* G1 Phase* Humans Leucine / pharmacology Phenotype S Phase* Thymidine / pharmacology Thymidylate Synthase / deficiency* Time Factors Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA21765/CA/NCI NIH HHS; CA32613/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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50-89-5/Thymidine; 61-90-5/Leucine; EC 2.1.1.45/Thymidylate Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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