DeWayne Roberts

Uptake as a determinant of methotrexate response in mouse leukemias.

Methotrexate-promoted survival of mice bearing different transplantable leukemias was compared with uptake of the drug by leukemia cells in vitro. A high degree of correlation (r2 = 0.88) showed that uptake may be a major determinant of the antitumor activity of methotrexate against transplantable mouse leukemias.

Dihydrofolate reductase activity and deoxynucleoside incorporation into DNA of human leukocytes. Relation to methotrexate administration

The effect of methotrexate on dihydrofolate reductase activity of normal and leukemic human leukocytes has been studied with folate as enzyme substrate. In a delayed effect, methotrexate increased dihydrofolate reductase activity in normal leukocytes and in chronic myelogenous leukemia. Enzyme activity was elevated in two of seven patients with chronic lymphocytic leukemia, but not in patients with acute leukemia. The administration of methotrexate inhibits the “drug‐induced” elevation of enzyme activity in normal leukocytes and in chronic myelogenous leukemia. The incorporation of deoxyuridine and thymidine into DNA was inhibited by methotrexate in childhood leukemia. In adults with leukemia, incorporation of deoxyuridine but not thymidine was inhibited. This difference beween adults and children, which must reflect a second effect of methotrexate, may occur as a result of the inhibition of purine synthesis in children.