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  • Title: Comparison of antineoplastic activity of 2',2'-difluorodeoxycytidine and cytosine arabinoside against human myeloid and lymphoid leukemic cells.
    Author: Bouffard DY, Momparler LF, Momparler RL.
    Journal: Anticancer Drugs; 1991 Feb; 2(1):49-55. PubMed ID: 1958852.
    Abstract:
    2',2'-difluorodeoxycytidine (known as dFdC, Gemcitabine and LY188011) is a new analog of deoxycytidine which has demonstrated excellent antineoplastic activity against many kinds of solid tumors and leukemic cell lines. We were interested in the comparison of the antineoplastic activity of this new antimetabolite with cytosine arabinoside (ARA-C) against HL-60 myeloid, RPMI-8392 B-lymphoid and Molt-3 T-lymphoid leukemic cell lines. Our in vitro experiments showed that dFdC was a more potent cytostatic drug than ARA-C against all the leukemic lines with IC50 ranging from 3 to 10 nM for dFdC and from 26 to 52 nM for ARA-C for a 48 h exposure. The cytotoxicity of both drugs was evaluated by clonogenic assay and dFdC was found to be 100 times more potent than ARA-C against all the leukemic cell lines for both a 2 h and a 24 h exposure. The recovery of DNA synthesis after drug removal was much slower for dFdC than for ARA-C. However, in contrast to cytostatic and cytotoxicity results ARA-C was a more potent inhibitor of DNA synthesis than dFdC for all the leukemic cell lines for short exposure. Uptake and elimination of the drugs showed that dFdC accumulated to a higher degree in the leukemic cells than ARA-C and that elimination of this difluoro analog was slower than that of ARA-C. These results indicate that dFdC has more potent in vitro antileukemic activity than ARA-C.
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