Effect of simultaneous AZT and hydroxyurea (HU): study in an HL-60 model system (Meeting abstract).

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Effect of simultaneous AZT and hydroxyurea (HU): study in an HL-60 model system (Meeting abstract).

Proc Annu Meet Am Soc Clin Oncol; 12:A15 1993. Unique Identifier : AIDSLINE ICDB/93694415
Nusbaum NJ; Joseph P; Lee Streich Flow Cytometry Lab., Hematology/Oncology Div.,; Brookdale Hosp. Medical Center, Brooklyn, NY 11212

Abstract: Patients (pts) with AIDS-related neoplasms may be considered for treatment with AZT, other antiretroviral agents, therapy for opportunistic infections, and/or cancer chemotherapy. These multiple medications are often poorly tolerated in this pt population, and so there is often interest in trying gentler chemotherapy than one might use in a similar cancer pt without HIV infection. It is suggested that, as protocols are designed that may expose AIDS pts simultaneously to multiple drugs that can affect DNA synthesis, the possibility of drug-drug interactions be carefully considered. In this regard, the current study explored the effect on HL-60 cells of exposure to AZT and/or HU, followed by resuspension of the cells in drug-free media. On the basis of wt, HU was considerably more toxic than AZT for the HL-60 line. As an example, 72-hr exposure to HU 0.1 mg/ml caused a marked drop in viable cell count, but with brisk growth resuming within a week in drug-free media. A combination of 0.1 mg/ml AZT and 0.1 mg/ml HU was only slightly more toxic than the single-agent HU. A single experiment with 48-hr drug exposure had suggested that there might be an element of negative synergy between the two drugs, but this isolated observation was refuted by multiple other experiments.

Keywords: Cell Division/DRUG EFFECTS Cell Line Cell Survival/*DRUG EFFECTS Dose-Response Relationship, Drug DNA Replication/DRUG EFFECTS Human Hydroxyurea/*PHARMACOLOGY Leukemia, Promyelocytic, Acute Tumor Cells, Cultured/*DRUG EFFECTS Zidovudine/*PHARMACOLOGY ABSTRACT
931230
M93C0814

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