EFFECT OF AGE IN CULTURE ON THE UPTAKE AND METABOLISM OF METHOTREXATE BY PRIMARY CULTURES OF HEPATOCYTES

  • 1 January 1979
    • journal article
    • research article
    • Vol. 24  (3) , 571-582
Abstract
Primary monolayer cultures of rat hepatocytes show an initial transient azide-sensitive capacity to concentrate methotrexate several-fold from the medium. After 48 h in culture they lose the azide-sensitive ability to accumulate methotrexate. The uptake of (+)5-methyltetrahydrofolate and folate was not altered greatly with time in culture and was unaffected by azide. Once inside the cell, methotrexate was converted predominantly to di- and triglutamate derivatives. After a short exposure to methotrexate (up to 4 h) most of the intracellular methotrexate was unaltered, but by 24 h nearly 80% was present as polyglutamates. Unlike the capacity of the cells to accumulate methotrexate, the ability of the cells to form polyglutamates did not appear to diminish with culture age.

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