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[Cancer Research 35, 1305-1308, May 1, 1975]
© 1975 American Association for Cancer Research
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Alteration of Methotrexate Uptake in Human Leukemia Cells by Other Agents

Richard A. Bender, Werner A. Bleyer, Shayla A. Frisby and Vincent T. Oliverio

Laboratory of Chemical Pharmacology, National Cancer Institute, Bethesda, Maryland 20014

The uptake of methotrexate (MTX) and the effect of drugs known to either inhibit or enhance MTX transport in L1210 murine leukemia were studied in man using blast cells from patients with acute myelogenous leukemia in vitro.

MTX uptake was found to proceed slowly, requiring at least 160 min for cells to reach a "steady state" when extracellular MTX concentrations were 1 µM. Efflux of MTX from preloaded cells required 80 to 120 min and the nonexchangeable or tightly bound fraction was 40% of the total intracellular drug.

Utilizing doses that are estimates of achievable peak blood levels following single i.v. injection, cephalothin (21 µg/ml) and hydrocortisone (20 µg/ml) inhibited net MTX accumulation by 20 and 28%, respectively. Vincristine sulfate at 8.3 and 0.083 µg/ml enhanced MTX uptake by 54 and 33%, respectively, by inhibiting MTX efflux, thus increasing the level of intracellular drug in excess of the tightly bound fraction. The potential clinical implications of using MTX in combination with the aforementioned drugs for cancer chemotherapy are discussed.

Received 9/23/74. Accepted 2/11/75.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1975 by the American Association for Cancer Research.