Abstract
Mechanism of action of cyclocytidine was examined in cultured cells (L5178Y). Cyclocytidine was active against the leukemia in vitro as well as in vivo and its IC50 was 0.041μg/ml, whereas that for aracytidine was 0.023μg/ml. This compound was also inhibited the thymidine incorporation into DNA and its IC50 was 110μg/ml, while that was 1.1μg/ml for aracytidine. Cyclocytidine itself was therefore considered to have no direct inhibitory effect. Since cyclocytidine seems to act in vitro as aracytidine after transformation, the factor influencing the transformation was examined and revealed to be only pH of the aqueous solution. Ratio of the transformantion under physiological conditions (pH7.3, 37°) was about 30 and 70% after 4 and 24 hr incubations, respectively.
