5-allyl-2'-deoxyuridine inhibition of nucleoside phosphorylase in HeLa cells containing mycoplasma.

Abstract

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.