The Lethality of Some d-Arabinosyl Nucleotides to Mouse Fibroblasts

A comparison has been made of the inhibitory and lethal effects of d-arabinosyl nucleosides and their corresponding nucleoside 5′-monophosphates on the viability of cultured mouse fibroblasts. The inhibition of cell multiplication is greater with 1-β-d-arabinofuranosylcytosine than with d-arabinosylcytosine 5′-monophosphate. Although either d-arabinosylcytosine 2′- or 3′-monophosphate is equally as effective as the 5′-nucleotide, no inhibition of cell multiplication was observed when cultures were treated with 2′,5′-cyclic arabinosylcytosine monophosphate. In contrast to these findings, it was found that d-arabinosyladenine 5′-monophosphate is a considerably more potent inhibitor of cell multiplication than is the parent nucleoside. Cells treated with 5-fluoro-2-deoxyuridine and 5-fluoro-2-deoxyuridine 5′-monophosphate show comparable lethality. However, 3′,5′-cyclic fluoro-2-deoxyuridine monophosphate did not inhibit cell multiplication. In all cases of inhibition of cell multiplication by nucleosides or nucleotides, the cells showed marked and progressive enlargement of cell volume.