Cytostatic and cytotoxic effects of (E)-2 '-deoxy-2 '-(fluoromethylene)-cytidine on a solid tumor and a leukemia cell line

(E)-2'-deoxy-2 '-(fluoromethylene)-cytidine (FMdC), a deoxycytidine analog displaying a very high toxicity toward a variety of solid tumor cell lines and xenografts, is activated intracellularly by deoxycytidine kinase (dCK). We have compared cytotoxicity of FMdC towards a human promyeolocytic leuke mia line HL-60 and a human colorectal carcinoma line COLO-205. Despite dCK activity being by far the highest in cells of lymphoid origin, the effects of FMdC were detectable at the lowest drug concentration only in a solid tu mor cell line, and at higher concentrations they were qualitatively similar in the two tumor Lines (increased cell protein content, cell cycle block a nd apoptosis). Apparently, low dCK activity in solid tumor cells sufficient ly activates FMdC to yield cytotoxic effects, while high dCK activity in le ukemia cells does not increase its cytotoxicity.