Abstract
Culture medium containing GAT protects human fibroblasts from MTX toxicity but does not prevent the accumulation of MTX poly-glutamates. FA competes with MTX for transport into cells and when added to the medium along with MTX prevents the accumulation of MTX polyglutamates. Confluent fibroblasts were co-incubated in MTX (10 μM) plus either GAT (glycine 0.67 mM, adenosine 37.5 μM, thymidine 41.3 μM) or FA (10 μM) or in MTX alone for 16 h. The cells were then re-fed MTX-free medium lacking all of the additions but containing 2.1 μM [3H] deoxyuridine and the incorporation of label into a trichloroacetic acid precipitate was determined. Untreated cells incorporated 122.9±23.1 nmoles dU/g protein/24 h (nm/g/24 h, n=3, x±S.D.). Cells preincubated in MTX (10 μM) alone incorporated 0.82±0.21 nm/g/24 h (n=3). Cells preincubated in MTX (10 μM) + GAT incorporated 1.11±0.18 nm/g/24h (n=3), whereas cells preincubated in MTX (10 μM) + FA (10 μM) incorporated 210.7±11.6 nm/g/24 h (n=3). Thus folinic acid reverses the effect of MTX when present along with MTX in the preincubation medium. GAT allows normal cell growth when present along with MTX in the preincubation medium. However, upon removal of GAT and MTX from these cells after a preincubation in both, cell growth and DNA synthesis remain suppressed.
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Rosenblatt, D., Whitehead, V., Matiaszuk, N. et al. 863 DIFFERENTIAL EFFECTS OF FOLINIC ACID (FA) AND GLYCINE, ADENOSINE, THYMIDINE (GAT) ON METHOTREXATE (MTX) TOXICITY IN CULTURED HUMAN CELLS. Pediatr Res 15 (Suppl 4), 586 (1981). https://doi.org/10.1203/00006450-198104001-00888
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DOI: https://doi.org/10.1203/00006450-198104001-00888