Inhibition of DNA methylation in Friend erythroleukemia cells by actinomycin D.
Actinomycin D caused the production of hypomethylated DNA in cultured Friend erythroleukemia cells at cell culture concentrations of 1-4 ng per ml. Inhibition of DNA methyltransferase in cell-free assays was kinetically complex, with mixed-type inhibition. Cornish-Bowden graphical analysis was used to derive a Ki of about 35 nmol Act D per mg DNA. Although nuclei from drug-treated cells were found to contain hypomethylated DNA and DNA methyltransferase could be extracted from the nuclei, the methyl-accepting ability of DNA in whole nuclei themselves was not elevated. We conclude that the low level of Act D bound to DNA in the nuclei is sufficient to prevent the remethylation of hypomethylated sites.
Kuykendall
J R
JR
Cancer Research Laboratory, Veterans Administration Medical Center, Memphis, TN 38104.
Cox
R
R
D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008837:Micrococcus / Q000235:genetics; D014407:Tumor Cells, Cultured
D003609:Dactinomycin; D004247:DNA; D008780:Methyltransferases