1987•Pediatric Hematology and OncologyRequires access
Action of Intermediate Doses of Methotrexate on Dihydrofolate Reductase in Malignant Diseases
Fotini Tzortzatou‐Stathopoulou, H. Zavitsa-Pateli, G. Mousatos, Neofytos Prodromou, M. Kairis, Joan M. Pappas
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Abstract
This report describes the effect of intermediate methotrexate (MTX) doses on dihydrofolate reductase (DHFR) activity in vivo in the leukocytes of 16 children with malignant diseases. The authors used a cytochemical technique, and the enzyme was studied in intact cells. The treatment protocols included MTX 500 mg-2 g/m2 weekly with leucovorin rescue. The above doses of MTX partially inhibit DHFR. The reduction of enzyme activity was observed in leukocytes within 24 h after MTX infusion, and it was more obvious in the polymorphonucleas and the monocytes. Complete inhibition of enzyme activity was not observed. These results do not agree with those of previous reports using biochemical techniques, which showed that small amounts of MTX inhibit DHFR activity. Even the large doses of MTX used in this study do not completely inhibit enzyme activity. It would be worthwhile to test the effect of even larger doses of MTX to find out if DHFR activity is inhibited.