Abstract
Preparations of α-2′-deoxythioguanosine (α-TGdR) completely free of β-2′-deoxythioguanosine (β-TGdR) were made and labeled with radiosulfur. A purified preparation of nucleoside phosphorylase obtained from human blood cells was found to be active on the β-anomer but completely inactive on the α-anomer. This property of the enzyme was used to characterize metabolites of α-TGdR. α-TGdR and β-TGdR were both found to be converted to the corresponding mono-, di-, and tri-phosphates and incorporated into the nucleic acids of Mecca lymphosarcoma cells in vivo. α-TGdR appeared predominantly in the terminal nucleoside positions of RNA and DNA. β-TGdR appeared predominantly in the nucleotide chain. Both Mecca lymphosarcoma and Ehrlich carcinoma cells formed significant quantities of analog nucleotides at all three levels of phosphorylation, probably exceeding the levels of guanine nucleotides in the cells for an appreciable time. The findings further support a correlation reported earlier between the incorporation of 6-thioguanine into DNA and the inhibition of cell growth.
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