| Lack of evidence for a high-affinity sarcosinamide carrier or a catecholamine carrier in Calu-1 lung-cancer cells, HT-29 colon-cancer cells, and DHF fibroblasts. | |
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MedLine Citation:
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PMID: 1280536 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously demonstrated that uptake of the amino acid amide sarcosinamide by the glioma cell line SK-MG-1 occurs via the catecholamine carrier that accommodates epinephrine (Km = 0.284 mM; Vmax = 0.154 nmol/10(6) cells/min). Sarcosinamide chloroethylnitrosourea (SarCNU), a new anticancer agent that exerts increased in vitro antitumor activity against gliomas as compared with BCNU (bis-chloroethylnitrosourea), the standard agent of choice, competitively inhibits sarcosinamide uptake by SK-MG-1 cells [inhibition constant (Ki) = 3.26 mM]. Using radiolabeled N-[3H]-sarcosinamide, we determined the transport of sarcosinamide in HT-29 colon-cancer cells, in Calu-1 lung-cancer cells, and in normal foreskin DHF fibroblasts. Sarcosinamide transport was linear for up to 1 min at 22 degrees C. In HT-29 cells and DHF fibroblasts, the uptake of sarcosinamide followed Michaelis-Menten kinetics of carrier-mediated transport. In HT-29 cells the Michaelis constant (Km) was 2.76 +/- 0.1 mM and the maximal velocity (Vmax) was 2.03 +/- 0.1 nmol/10(6) cells/min, whereas in DHF fibroblasts the respective values were 6.58 +/- 3.90 mM and 12.08 +/- 8.20 nmol/10(6) cells/min. In these two cell lines, neither epinephrine nor leucine significantly reduced sarcosinamide transport. In Calu-1 cells there was no evidence of carrier-mediated transport of either sarcosinamide or epinephrine. These nonglial cell lines lack a high-affinity catecholamine carrier. The increased cytotoxicity of SarCNU in gliomas may correlate with the presence of a high-affinity catecholamine carrier. |
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Authors:
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A Malapetsa; J L Bramson; A J Noë; L C Panasci |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 31 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 1992 |
Date Detail:
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Created Date: 1992-12-31 Completed Date: 1992-12-31 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: GERMANY |
Other Details:
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Languages: eng Pagination: 146-50 Citation Subset: IM |
Affiliation:
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Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport Colonic Neoplasms / metabolism Drug Carriers Epinephrine / pharmacokinetics* Fibroblasts / metabolism Humans Lung Neoplasms / metabolism Sarcosine / analogs & derivatives*, pharmacokinetics Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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R01-NSC22230/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Drug Carriers; 107-97-1/Sarcosine; 51-43-4/Epinephrine; 6250-76-6/N-methylglycinamide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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