This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Flatau, E Articles by Jones, P A Search for Related Content PubMed PubMed Citation Articles by Flatau, E Articles by Jones, P A

 Previous Article  |  Next Article 

Mol Cell Biol. 1984 October; 4(10): 2098-2102

DNA methylation in 5-aza-2'-deoxycytidine-resistant variants of C3H 10T1/2 C18 cells.

ABSTRACT

A cell line (T17) was derived from C3H 10T1/2 C18 cells after 17 treatments with increasing concentrations of 5-aza-2'-deoxycytidine. The T17 cell line was very resistant to the cytotoxic effects of 5-aza-2'-deoxycytidine, and the 50% lethal dose for 5-aza-2'-deoxycytidine was ca. 3 microM, which was 30-fold greater than that of the parental C3H 10T1/2 C18 cells. Increased drug resistance was not due to a failure of the T17 cell line to incorporate 5-aza-2'-deoxycytidine into DNA. The cells were also slightly cross-resistant to 5-azacytidine. The percentage of cytosines modified to 5-methylcytosine in T17 cells was 0.7%, a 78% decrease from the level of 3.22% in C3H 10T1/2 C18 cells. The DNA cytosine methylation levels in several clones isolated from the treated lines were on the order of 0.7%, and clones with methylation levels lower than 0.45% were not obtained even after further drug treatments. These highly decreased methylation levels appeared to be unstable, and DNA modification increased as the cells divided in the absence of further drug treatment. The results suggest that it may not be possible to derive mouse cells with vanishingly low levels of 5-methylcytosine and that considerable de novo methylation can occur in cultured lines.

This article has been cited by other articles:

• Yoo, C. B., Jeong, S., Egger, G., Liang, G., Phiasivongsa, P., Tang, C., Redkar, S., Jones, P. A. (2007). Delivery of 5-Aza-2'-Deoxycytidine to Cells Using Oligodeoxynucleotides. Cancer Res. 67: 6400-6408 [Abstract] [Full Text]  
• Loriot, A., De Plaen, E., Boon, T., De Smet, C. (2006). Transient Down-regulation of DNMT1 Methyltransferase Leads to Activation and Stable Hypomethylation of MAGE-A1 in Melanoma Cells. J. Biol. Chem. 281: 10118-10126 [Abstract] [Full Text]  
• Shevchuk, T., Kretzner, L., Munson, K., Axume, J., Clark, J., Dyachenko, O. V., Caudill, M., Buryanov, Y., Smith, S. S. (2005). Transgene-induced CCWGG methylation does not alter CG methylation patterning in human kidney cells. Nucleic Acids Res 33: 6124-6136 [Abstract] [Full Text]  
• Shen, D.-H., Chan, K. Y.-K., Khoo, U.-S., Ngan, H. Y.-S., Xue, W.-C., Chiu, P.-M., Ip, P., Cheung, A. N.-Y. (2005). Epigenetic and genetic alterations of p33ING1b in ovarian cancer. Carcinogenesis 26: 855-863 [Abstract] [Full Text]  
• Cheng, J. C., Weisenberger, D. J., Gonzales, F. A., Liang, G., Xu, G.-L., Hu, Y.-G., Marquez, V. E., Jones, P. A. (2004). Continuous Zebularine Treatment Effectively Sustains Demethylation in Human Bladder Cancer Cells. Mol. Cell. Biol. 24: 1270-1278 [Abstract] [Full Text]  
• Wang, Y., Fang, M. Z., Liao, J., Yang, G.-Y., Nie, Y., Song, Y., So, C., Xu, X., Wang, L.-D., Yang, C. S. (2003). Hypermethylation-Associated Inactivation of Retinoic Acid Receptor {beta} in Human Esophageal Squamous Cell Carcinoma. Clin. Cancer Res. 9: 5257-5263 [Abstract] [Full Text]  
• Chan, H.-W., Kurago, Z. B., Stewart, C. A., Wilson, M. J., Martin, M. P., Mace, B. E., Carrington, M., Trowsdale, J., Lutz, C. T. (2003). DNA Methylation Maintains Allele-specific KIR Gene Expression in Human Natural Killer Cells. J. Exp. Med. 197: 245-255 [Abstract] [Full Text]  
• Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes Dev. 16: 6-21 [Full Text]  
• Panning, B, Jaenisch, R (1996). DNA hypomethylation can activate Xist expression and silence X-linked genes.. Genes Dev. 10: 1991-2002 [Abstract]  
• Gounari, F, Banks, G R, Khazaie, K, Jeggo, P A, Holliday, R (1987). Gene reactivation: a tool for the isolation of mammalian DNA methylation mutants.. Genes Dev. 1: 899-912 [Abstract]  
• Holliday, R (1987). The inheritance of epigenetic defects. Science 238: 163-170 [Abstract]