Potentiation of methotrexate toxicity by dipyridamole

Dipyridamole, an inhibitor of facilitated transport systems for purines and pyrimidines, was shown to enhance the toxicity of methotrexate (MTX) against cells in culture and in mice. Under certain incubation conditions, the availability of performed purines and pyrimidines in undialyzed serum appear...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1984-06, Vol.44 (6), p.2493-2496
Main Authors: NELSON, J. A, DRAKE, S
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Cell Line
Cell Survival - drug effects
Cricetinae
Cricetulus
Dipyridamole - administration & dosage
Dipyridamole - toxicity
DNA Replication - drug effects
Drug Synergism
Female
General aspects
Kinetics
Leukemia L1210 - drug therapy
Medical sciences
Methotrexate - administration & dosage
Methotrexate - toxicity
Mice
Mice, Inbred AKR
Mice, Inbred Strains
Osteosarcoma - drug therapy
Ovary
Pharmacology. Drug treatments
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Summary:Dipyridamole, an inhibitor of facilitated transport systems for purines and pyrimidines, was shown to enhance the toxicity of methotrexate (MTX) against cells in culture and in mice. Under certain incubation conditions, the availability of performed purines and pyrimidines in undialyzed serum appeared to render Chinese hamster ovary cells insensitive to MTX. Addition to the culture of nontoxic levels of dipyridamole conferred sensitivity to MTX. Inhibition of [3H]thymidine uptake by dipyridamole paralleled the enhanced MTX toxicity in a comparison of the dose-effect relationships. Inhibition of [3H]hypoxanthine uptake also occurred, although approximately 10-fold higher levels of dipyridamole were required. In vivo dipyridamole enhanced MTX toxicity in mice; however, the antitumor activity of MTX toward Ridgway osteogenic sarcoma and L1210 leukemia was not dramatically improved.
ISSN:0008-5472
1538-7445