3'-AZIDO-3'-DEOXYTHYMIDINE POTENTLY INHIBITS PROTEIN GLYCOSYLATION - A NOVEL MECHANISM FOR AZT CYTOTOXICITY

3'-Azido-3'-deoxythymidine (AZT) is one of the primary chemotherapeuti c agents used in the treatment of human immunodeficiency virus (HIV) i nfection. Unfortunately, AZT therapy is accompanied by severe side eff ects. Using Golgi-enriched membrane fractions, we have determined that 3'-azido-3'-deoxythymidine monophosphate, the primary AZT metabolite in treated cells, potently inhibits protein glycosylation. This inhibi tion results from direct competition with several pyrimidine-sugars fo r transport into Gels membranes. This potential mechanism of cytotoxic ity does not involve 3'-azido-3'-deoxythymidine triphosphate, the AZT metabolite most likely responsible for its antiviral effects; thus, it may be possible to develop novel therapeutic strategies that prevent inhibition of glycosylation without affecting the anti-HIV properties of AZT.