Decreased folylpolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines.
نویسندگان
چکیده
منابع مشابه
Decreased folylpolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines.
Determinants of methotrexate (MTX) resistance in cell lines resistant to short, but not continuous, MTX exposure were investigated since such lines may have relevance to clinical resistance. CCRF-CEM R30dm (R30dm), cloned from CCRF-CEM R30/6 (a MTX-resistant subline of the CCRF-CEM human leukemia cell line), had growth characteristics similar to CCRF-CEM. R30dm was resistant to a 24-h exposure ...
متن کاملMechanism of Fluorouracil Resistance Decreased Folylpolyglutamate Synthetase Expression: A Novel
HCT-8 cells become rapidly resistant to either 4-h (HCT-8/4hR) or 7-day (HCT-8/7dR) repeated exposures to fluorouracil (FUra). The HCT8/7dR cells were studied in more detail to determine their mechanism of resistance to FUra. Thymidylate synthase activity, binding of 5-fluorodeoxyuridylate to thymidylate synthase, and incorporation of FUra into RNA were not different between the parental and re...
متن کاملMethotrexate and Cytosine Arabinoside Modulation of Thymidylate Synthetase Activity in CCRF-CEM Cells1
Thymidylate synthetase activity of a human lymphoblastic cell line, CCRF-CEM, was elevated by the addition of methotrexate to the culture medium and was lowered when cytosine arabinoside was added. The simultaneous addition of both drugs resulted in levels of enzyme activity intermediate between those observed for each drug alone. The level of enzyme activity could be modulated by varying the r...
متن کاملMethotrexate and cytosine arabinoside modulation of thymidylate synthetase activity in CCRF-CEM cells.
Thymidylate synthetase activity of a human lymphoblastic cell line, CCRF-CEM, was elevated by the addition of methotrexate to the culture medium and was lowered when cytosine arabinoside was added. The simultaneous addition of both drugs resulted in levels of enzyme activity intermediate between those observed for each drug alone. The level of enzyme activity could be modulated by varying the r...
متن کاملLYMPHOID NEOPLASIA Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia
Folylpoly-gluatamate synthetase (FPGS) catalyzes the polyglutamylation and thus intracellular retention of folates and antifolates (eg, methotrexate; MTX) through the addition of multiple glutamate equivalents to their -carboxyl residue. Since polyglutamylation of antifolates is crucial for their pharmacological activity in leukemia, loss of FPGS function results in decreased cellular levels of...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1991
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(18)38101-8