Methotrexate 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 ratio of the two drugs. The ratio of enzyme activity in homogenates of cells from control or drug-treated cultures remained constant with dialysis. Changes in the rate of thymidylate synthetase turnover are suggested as the basis for the variation of enzyme activity in the drug-treated cultures.