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5-Allyl-2'-deoxyuridine Inhibition of Nucleoside Phosphorylase in HeLa Cells Containing Mycoplasma¹

Department of Medicine A, Roswell Park Memorial Institute, New York State Department of Health, and the Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14203

5-Allyl-2'-deoxyuridine (AUdR) inhibits nucleoside phosphorylase activity associated with mycoplasma-contaminated HeLa (HeLa/PPLO) cells. This has been demonstrated in cell culture experiments in which AUdR allowed thymidine to support HeLa/PPLO growth in a system dependent upon thymidine, in which, because of phosphorolytic catabolism, thymidine alone had been unable to do so. Inhibition of the exaggerated nucleoside phosphorylase activity of HeLa/PPLO by AUdR restored the chemotherapeutic activity of 5-fluoro-2'-deoxyuridine on these cells. In experiments with isotopically labeled deoxynucleosides, AUdR inhibited nucleoside catabolism by HeLa/PPLO, by a mycoplasma culture, and by purified horse liver thymidine phosphorylase.

Lesser inhibition of nucleoside phosphorylase activity in one or more of these systems was obtained with N-3-methylthymidine, N-3-methyluridine, 5-trifluoromethyl-2'-deoxyuridine, and other 5-substituted 2'-deoxyuridines.

AUdR showed no biologic activity other than inhibiting nucleoside phosphorylase, a specificity that recommends its further investigation as an adjuvant compound in circumstances where inhibition of phosphorolytic destruction of nucleoside substrates or drugs is desirable.

¹ This investigation was supported in part by Research Grant No. T-231 from the American Cancer Society and by USPHS Research Grant Nos. CA 2857 and CA 5834 from the National Cancer Institute.

Received 10/ 6/66. Accepted 6/12/67.