Some effects of D-arabinosyl nucleosides on polymer syntheses in mouse fibroblasts.

The effects of l-/3-i>-arabinofuranosylcytosine and of 9-/3-Uarabmofuranosyladenine have been studied on the growth and multiplication of mouse fibroblasta in suspended cell culture. Both compounds i>ermit a considerable enlargement of the cells but sharply inhibit multiplication. The effects of these agents on the syntheses of DXA, RXA, and protein in these cells have also been examined. Both chemicals markedly inhibit DNA synthesis and reduce the cloning capacity of the cultures. No significant effect of either comixnind has been detected on RXA synthesis. A slight inhibition of protein synthesis has been ob served with arabinosyladenine. After prolonged inhibition of cell multiplication by either compound, washed cells, incubated in the normal medium supplemented with thymidine-2-uC, were able to synthesize DXA at an approximately normal rate for 6 hr. After this time, DXA synthesis stopped abruptly and cell division occurred in 50-80% of the cells. It has been concluded that inhibition of DXA synthesis and of cell multiplication by D-arabinosyl nucleosides is probably not attributable to irrevers ible lesions in the DNA resulting from terminal addition of D-arabinosyl nucleotides.