Induction of resistance to 1-beta-D-arabinofuranosylcytosine in human H9 cell line by simian immunodeficiency virus.
We examined drug sensitivity of human T cell acute lymphoblastic leukemia H9 cells chronically infected with simian immunodeficiency virus (SIVmac) and found that the retrovirus-infected H9 cells showed 8.2-fold resistance to 1-beta-D-arabinofuranosylcytosine (Ara-C). In the infected cells, Ara-CTP levels decreased to 20% of that found in uninfected H9 cells after 3 h incubation at Ara-C concentration of 1 microM, and 8.1-fold increase of cytidine deaminase activity was observed in the infected H9 cells. A competitive inhibitor of cytidine deaminase, 3, 4, 5, 6-tetrahydrouridine (THU), at 100 microM reversed Ara-C resistance in the infected cells. These results indicate that inducing increased cytidine deaminase activity by SIVmac infection conferred Ara-C resistance to H9 cells. An understanding of these cellular differences in drug sensitivity may aid in the development of therapeutic strategies against retrovirus-infected cells.
Yusa
K
K
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Oh-hara
T
T
Tsuruo
T
T
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000633:toxicity*; D003564:Cytidine Deaminase / Q000378:metabolism; D004351:Drug Resistance; D005472:Fluorouracil / Q000633:toxicity; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell; D015122:Mercaptopurine / Q000633:toxicity; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013767:Tetrahydrouridine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000633:toxicity; D016047:Zalcitabine / Q000633:toxicity; D015215:Zidovudine / Q000633:toxicity
D003561:Cytarabine; D013767:Tetrahydrouridine; D015215:Zidovudine; D016047:Zalcitabine; D015122:Mercaptopurine; D003564:Cytidine Deaminase; D014740:Vidarabine; D005472:Fluorouracil