Induction of internucleosomal DNA fragmentation in human myeloid leukemia cells by 1-beta-D-arabinofuranosylcytosine.
The present results demonstrate that treatment of human U-937 myeloid leukemia cells with 1-beta-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.
Gunji
H
H
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Kharbanda
S
S
Kufe
D
D
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D012334:RNA, Neoplasm / Q000302:isolation & purification
D004273:DNA, Neoplasm; D009707:Nucleosomes; D012334:RNA, Neoplasm; D003561:Cytarabine