Abstract
The purpose of this study was to elucidate the mechanism of 201Thallium-chloride (201Tl) uptake in tumor cells and its possible relationship to potassium channels. The subcellular biodistribution of 201Tl in tumor cells was examined in colon cancer (LS180) bearing nude mice using sequential centrifugation. The involvement of potassium channels in 201Tl uptake in tumor cells was examined by uptake inhibition with potassium channel blockers (ouabain, bumetanide, and glibenclamide) in cultured leukemia cells (K562). Greater than 90% of 201Tl was found in the soluble cytoplasmic fraction. 201Tl uptake was inhibited by ouabain and bumetanide but not by glibenclamide. These data demonstrate that 201Tl uptake in tumor cells is mediated by the Na(+)-K+ ATPase and the Na(+)-K(+)-2Cl- cotransporter with 201Tl acting as a potassium analogue.
MeSH terms
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Adenosine Triphosphate / metabolism
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Animals
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Biological Transport / drug effects
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Bumetanide / pharmacology
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Carrier Proteins / metabolism
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Cell Nucleus / chemistry
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Chlorides / pharmacokinetics*
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Colonic Neoplasms / chemistry*
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Colonic Neoplasms / diagnostic imaging
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Colonic Neoplasms / enzymology
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Cytoplasm / chemistry
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Diuretics / pharmacology
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Enzyme Inhibitors / pharmacology
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Glyburide / pharmacology
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Humans
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Hypoglycemic Agents / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Microsomes / chemistry
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Mitochondria / chemistry
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Neoplasm Transplantation
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Ouabain / pharmacology
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Potassium Channels / metabolism*
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Sodium-Potassium-Chloride Symporters
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Sodium-Potassium-Exchanging ATPase / metabolism
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Thallium Radioisotopes / pharmacokinetics*
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Tomography, Emission-Computed, Single-Photon
Substances
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Carrier Proteins
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Chlorides
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Diuretics
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Enzyme Inhibitors
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Hypoglycemic Agents
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Potassium Channels
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Sodium-Potassium-Chloride Symporters
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Thallium Radioisotopes
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Bumetanide
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Ouabain
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Adenosine Triphosphate
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Sodium-Potassium-Exchanging ATPase
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Glyburide