Modulation of cytosine arabinoside-induced proliferation inhibition by exogenous adenosylmethionine.

The effect of cytosine arabinoside on adenosylmethionine synthesis in relation to its proliferation-inhibiting ability was investigated in HT/29 and SW 620 human colon-tumor cell lines. A significant decrease in adenosylmethionine synthetase (E. C.2.4.2.13) activity was found after 2.5 h incubation with the drug, suggesting that depletion of adenosylmethionine pools might occur. Both this possible loss of adenosylmethionine and the cytostatic effect of cytosine arabinoside could partly be reversed by the exogenous administration of the former drug. Our data show that the cytostatic effect of cytosine arabinoside may be due in part to a shortage of adenosylmethionine; this finding is important for the design of combination chemotherapy regimens.