Abstract
The modulating effects of leucovorin on the synthesis of methotrexate (MTX) polyglutamates in the MCF-7 human breast cancer cell line have been investigated using a paired-ion high performance liquid chromatography (HPLC) system. Leucovorin decreased the intracellular level of MTX and profoundly affected polyglutamate synthesis irrespective of whether it was administered with or after MTX. Inhibition of MTX polyglutamate synthesis was also observed when concentrations of leucovorin too low to affect intracellular levels of MTX were employed. Leucovorin did not promote efflux of MTX from the MCF-7 cells and did not affect the distribution of the retained drug amongst the various polyglutamate forms.
Original language | English (US) |
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Pages (from-to) | 2897-2903 |
Number of pages | 7 |
Journal | Biochemical Pharmacology |
Volume | 34 |
Issue number | 16 |
DOIs | |
State | Published - Aug 15 1985 |
Externally published | Yes |