Abstract
4'-Thioadenosine (4'-SAdo) is an adenosine analog with the bridge oxygen in the ribose replaced by a sulfur atom. 4'-SAdo is cytostatic to the HL-60 cells in concentrations up to 25 μM after four days, within which the HL-60 cells can be induced to differentiate in a dose-dependent manner, as judged by their ability to reduce nitroblue tetrazolium. 4'-SAdo is cytotoxic to the HL-60 cells at 40 μM after four days. The ability of 4'-SAdo to induce HL-60 differentiation may be related to its ability to inhibit potently S-adenosylhomocysteine hydrolase (AdoHcy hydrolase), leading ultimately to the accumulation of AdoHcy with an attendant inhibition of cellular transmethylation reactions. HL-60 cells treated with 4'-SAdo show a decrease in the levels of ADP + ATP, but without any change in GDP + GTP. Interestingly, two unknown nucleoside products appear in a dose-dependent manner in the HL-60 cells treated with 4'-SAdo.
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