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Selective Destruction of Cultured Tumor Cells with Uncontrolled Nuclear Division by Cytochalasin B and Cytosine Arabinoside¹

Departments of Microbiology and Pathology, University of Utah Medical Center, Salt Lake City, Utah 84112, and Veterans Administration Hospital, Department of Research, Salt Lake City, Utah 84113

Cultures of normal human and hamster and malignant human and hamster cells respond to cytochalasin B (CB) differently. The neoplastic cells become highly multinucleated with continuous nuclear division, while cytoplasmic division is prevented. These cells exhibit uncontrolled nuclear division. The normal cells show control of nuclear division, since CB treatment results in only binucleation, although cytoplasmic division is prevented. The CB-treated normal cells also show reduced incorporation of [³H]thymidine. When rapidly growing normal or neoplastic cells of either species are treated with cytosine arabinoside (ara-C), all cells are killed within 10 to 20 days. If the normal cells are treated with ara-C in the presence of CB, the cells survive for at least 35 to 40 days, suggesting that CB can protect normal cells from the destructive effects of ara-C. However, if malignant cells are treated with ara-C in the presence of CB, all cells are destroyed in 25 days. Although CB affords some protection to tumor cells, it is relatively small and appears only to effect a delay in ultimate cell death. Treatment of any of the cell lines with CB alone results in some loss of viability, but the drug is reversible although less so for the malignant cells.

In additional experiments, ara-C- plus CB-treated normal and neoplastic cells were reversed from the drugs and propagated in normal medium at various periods after the initiation of ara-C treatment. ara-C- plus CB-treated normal cells could be freely reversed at any time after the start of ara-C treatment, up to at least 35 days. After reversal, cell growth resumed, and the total number of cells returned to that present prior to drug treatment. The tumor cells could not be freely reversed from ara-C plus CB, even when the ara-C was present for only 5 days. In this case the cells seemed to be destroyed at the same rate as in cultures where both drugs were kept in the medium. These results suggest that CB can protect normal but not malignant cells from the toxic effects of ara-C and offer a method to specifically destroy tumor cells.

¹ Supported by National Cancer Institute Grant CA-15141 and Intramural Research Funds of the Salt Lake City, Utah, Veterans Administration Hospital.

Received 4/28/75. Accepted 8/ 7/75.