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Synergistic cytotoxicity of AZT plus alpha and gamma interferon in chronic myeloid leukemia cell line K562 *
Author(s) -
Tosi Patrizia,
Visain Giuseppe,
Ottaviani Emanuela,
Gamberi Barbara,
Cenacchi Annarita,
Tura Sante
Publication year - 1993
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1993.tb00632.x
Subject(s) - cytotoxicity , k562 cells , myeloid leukemia , zidovudine , thymidine , alpha interferon , dna synthesis , cell culture , interferon , in vitro , thymidylate synthase , pharmacology , leukemia , cytotoxic t cell , interferon alfa , biology , immunology , medicine , chemotherapy , biochemistry , virus , fluorouracil , viral disease , genetics
We have previously reported that the antineoplastic activity of 3′ ‐azido 3′ deoxythymidine (AZT) can be increased by drugs that inhibit “ de novo ” thymidylate synthesis, such as 5‐fluorouracil, methotrexate and hydroxyurea. In the present study we tested the combinations AZT + alpha interferon (IFN) and AZT + gamma IFN on in vitro growth of the human acute‐phase chronic myeloid leukemia (CML) cell line K562. After 72 hours incubation, not only AZT + α‐IFN but also AZT + γ‐IFN were synergistic in inhibiting K562 growth, as demonstrated by isobologram analysis of the data. This enhanced cytotoxicity was confirmed by the evaluation of [3H]AZT incorporation into cellular DNA, that was increased by 50% and 222% in the presence of α‐ and γ‐IFN, respectively. The addition of 50 μmol/l thymidine to the culture medium was able to reduce the cytotoxicity of the drug combinations to the degree observed with each compound alone; furthermore, the increased incorporation of AZT into DNA was completely reversed. These data indicate the existence of a biochemical interaction between AZT and IFNs that results in an increased cytotoxic effect. While the combination AZT + α‐IFN is currently being tested in HIV‐related malignancies, AZT + γ‐IFN is new and deserves further study in human CML acute and chronic phase models, in view of possible clinical applications.