TY - JOUR
T1 - Effects of sodium butyrate and 5-azacytidine on DNA methylation in human tumor cell lines
T2 - Variable response to drug treatment and withdrawal
AU - Cosgrove, Dominic E.
AU - Cox, G. Stanley
N1 - Funding Information:
This work was supportedb y a grant from the NebraskaD epartmenotf Health( 87-06)W. e thankt he followingin vestigatofrosr supplyingu s with tumorc ell lines:D . Johnson(I M-9), R. Pattillo( JAr), B. Weintraub (CBT and ChaGo);a ndt heg enerougsi ftso f Drosophila melanogastDeNr A from C. Delidakisa ndJ.J. Bonner are gratefullay cknowledgeTdh. e expertp reparatioonf this manuscripbty PamelaW altera ndElinor Shanahan is sincerelya ppreciated.
PY - 1990/9/10
Y1 - 1990/9/10
N2 - The effect of butyrate (Btr) and 5-azacytidine (azaC) on genomic DNA methylation was examined in a variety of human tumor cell lines. Butyrate treatment differentially affected 5-methylcytosine (m5C) content in a cell type-specific manner. For example, incubation of CBT cells (glioblastoma multiforme) for 48 h in medium containing 2 mM Btr resulted in the hypomethylation of their DNA; after removal of the drug, the m5C content was rapidly (24 h) restored to its original level. In contrast, when HeLa cells (cervical carcinoma) were cultured for 48 h in 3 mM Btr, their genomic DNA became more extensively methylated relative to the untreated control, and the hypermethylated state was maintained for long periods in culture. Treatment of HeLa cell lines with azaC resulted in extensive demethylation of their DNA. Following removal of the drug, the DNA was rapidly remethylated to levels equal to or greater than those of the untreated cells. The hypermethylated state has remained stable for over 180 generations. Together, the data suggest that cells respond rapidly to alter drug-induced reductions in the m5C content of their DNA, and this response can subsequently result in overmethylation. In contrast, when drug-induced hypermethylation of genomic DNA occurs, it may persist for many cell generations.
AB - The effect of butyrate (Btr) and 5-azacytidine (azaC) on genomic DNA methylation was examined in a variety of human tumor cell lines. Butyrate treatment differentially affected 5-methylcytosine (m5C) content in a cell type-specific manner. For example, incubation of CBT cells (glioblastoma multiforme) for 48 h in medium containing 2 mM Btr resulted in the hypomethylation of their DNA; after removal of the drug, the m5C content was rapidly (24 h) restored to its original level. In contrast, when HeLa cells (cervical carcinoma) were cultured for 48 h in 3 mM Btr, their genomic DNA became more extensively methylated relative to the untreated control, and the hypermethylated state was maintained for long periods in culture. Treatment of HeLa cell lines with azaC resulted in extensive demethylation of their DNA. Following removal of the drug, the DNA was rapidly remethylated to levels equal to or greater than those of the untreated cells. The hypermethylated state has remained stable for over 180 generations. Together, the data suggest that cells respond rapidly to alter drug-induced reductions in the m5C content of their DNA, and this response can subsequently result in overmethylation. In contrast, when drug-induced hypermethylation of genomic DNA occurs, it may persist for many cell generations.
KW - (Human)
KW - 5-Azacytidine
KW - DNA methylation
KW - Sodium butyrate
KW - Tumor cell line
KW - genomic DNA
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U2 - 10.1016/0167-4781(90)90124-K
DO - 10.1016/0167-4781(90)90124-K
M3 - Article
C2 - 1698097
AN - SCOPUS:0025145509
SN - 0167-4781
VL - 1087
SP - 80
EP - 86
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
IS - 1
ER -