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Induction of Internucleosomal DNA Fragmentation in Human Myeloid Leukemia Cells by 1-ß-D-Arabinofuranosylcytosine¹

Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

The present results demonstrate that treatment of human U-937 myeloid leukemia cells with 1-ß-D-arabinofuranosylcytosine (ara-C) is associated with DNA fragmentation at multiples of approximately 200 base pairs. The extent of ara-C-induced DNA fragmentation was dependent on drug concentration and time of exposure. This pattern of internucleosomal DNA cleavage has been observed during programmed cell death and was associated in the present studies with loss of clonogenic survival. The results also demonstrate that the c-jun protooncogene is induced by ara-C during periods of DNA cleavage. These findings suggest that ara-C activates a program involving both oligonucleosomal DNA fragmentation and changes in early response gene expression.

¹ This investigation was supported by USPHS Grant CA29431 awarded by the National Cancer Institute, Department of Health and Human Services, and by a Burroughs Wellcome Award in Clinical Pharmacology (D. K.).

Received 11/ 8/90. Accepted 11/26/90.

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