TY - JOUR T1 - Lack of Intracellular Conversion of Dihydrohomofolate to Tetrahydrohomofolate in Leukemia Cells with High Levels of Dihydrofolate Reductase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 353 LP - 361 VL - 8 IS - 3 AU - ALY NAHAS AU - MORRIS FRIEDKIN Y1 - 1972/05/01 UR - http://molpharm.aspetjournals.org/content/8/3/353.abstract N2 - The uptake of tritium-labeled dihydrohomofolate was investigated with intact leukemia cells, known to be either sensitive or resistant to amethopterin. Comparable experiments were carried out with H2-folate. Chromatography to DEAE-cellulose was used to determine possible intracellular conversion of H2-homofolate to H4-homofolate, whereas microbiological assays were utilized for uptake studies of H2-folate and conversion to H4-folate. The amethopterin-resistant cells showed a higher uptake of H2-folate and a higher intracellular conversion of H2-folate to H4-folate than the sensitive cells, consistent with high H2-folate reductase activity in lysates of resistant cells. The situation with H2-homofolate was quite different. Uptake of H2-homofolate by sensitive and resistant cells was almost the same, with no detectable intracellular conversion of H2-homofolate to H4-homofolate, despite the fact that H2-homofolate is an excellent substrate of H2-folate reductase. ACKNOWLEDGMENT We wish to thank Dr. Roy L. Kisliuk for valuable advice about microbiological assays as well as for critical evaluation of the design of the experiments described herein. ER -