Effects of thiol compounds on methotrexate uptake by murine lymphocytes from thymus and thymic lymphosarcoma.
The characteristics of methotrexate (MTX) uptake and the effects of exogenous sulfhydryl compounds (i.e. reduced glutathione and cysteine) on MTX accumulation in thymocytes and thymic lymphosarcoma cells has been studied. Significant differences in the rate and the extent of MTX uptake between normal and neoplastic cells were demonstrated. MTX accumulation was found to be more efficient in thymic lymphosarcoma cells as compared with parental cells. In the cells examined, MTX uptake was not affected by membrane impermeable GSH. In contrast, short-term exposure to cysteine revealed heterogeneity in MTX uptake systems between normal and neoplastic thymocytes. Thus, cysteine was demonstrated to enhance the rate and extent of MTX accumulation exclusively in thymic lymphosarcoma cells. The results obtained indicate that in neoplastic thymocytes biochemical changes had developed in the membrane redox state around the MTX uptake system. These alterations are chemically distinguishable by their characteristic response to cysteine. The findings suggest that the plasma membrane changes could be exploited for preferential enhancement of MTX uptake by neoplastic thymocytes.
Soltysiak-Pawluczuk
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Department of Pharmacology, Institute of Drug Research and Control, Warsaw, Poland.
Naciazek-Wieniawska
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Danysz
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Czarnomska
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D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003545:Cysteine / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D005978:Glutathione; D003545:Cysteine; D008727:Methotrexate