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Dihydrofolate reductase activity and deoxynucleoside incorporation into DNA of human leukocytes. Relation to methotrexate administration
Author(s) -
Roberts Dewayne,
Hall Thomas C.
Publication year - 1967
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(1967)20:5<905::aid-cncr2820200553>3.0.co;2-g
Subject(s) - dihydrofolate reductase , methotrexate , leukemia , deoxyuridine , medicine , chronic myelogenous leukemia , enzyme , thymidine , pharmacology , acute lymphocytic leukemia , purine , dna synthesis , chronic lymphocytic leukemia , biochemistry , dna , immunology , biology , lymphoblastic leukemia
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.