Abstract:
:3'-Azido-3'-deoxythymidine (AZT) competitively inhibited the transport of thymidine (Km = 0.23 mM) into human erythrocytes with a Ki of 1.0 mM at 37 degrees C. The principal human metabolite of AZT in plasma, the 5'-glucuronide (GAZT), was a weak inhibitor of the nucleoside transporter (< 20% inhibition of the influx of 1.0 microM thymidine by 10 microM GAZT). The minor AZT metabolite, 3'-amino-3'-deoxythymidine (AMT), competitively inhibited thymidine transport with a Ki of 9.1 mM. The influx of AMT into human erythrocytes was found to be a saturable process (Km = 12 mM) that was largely inhibited by dilazep, thus indicating that AMT influx occurs via the nucleoside transporter. High extracellular concentrations of AZT may contribute to the synergistic cytotoxicity of AZT plus either 5-fluorouracil or methotrexate by inhibiting thymidine transport into cancer cells whose de novo biosynthesis of dTMP is impaired pharmacologically or by inhibiting efflux of 2'-deoxy-5-fluorouridine and/or 2'-deoxyuridine from these cells.
journal_name
Oncol Resjournal_title
Oncology researchauthors
Zimmerman TP,Domin BA,Mahony WBsubject
Has Abstractpub_date
1993-01-01 00:00:00pages
483-7issue
12eissn
0965-0407issn
1555-3906journal_volume
5pub_type
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