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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shapiro, L. J. Mohandas, T. Jones, P. A. Taylor, S. M. |
| Abstract | Three cytidine analogs containing modifications in the 5-position of the cytosine ring (5-azacytidine, 5-aza-2'-deoxycytidine and pseudoisocytidine) induced the expression of human hypoxanthine/guanine phosphoribosyltransferase (IMP; pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) gene (HPRT) from a structurally normal inactive human X chromosome retained in a mouse-human somatic cell hybrid. Between 0.1% and 8% of the cells surviving treatment with these analogs were able to form colonies in selective medium (hypoxanthine/aminopterin/thymidine/glycine medium), but two other analogs, 5-fluoro-2'-deoxycrytidine and 5.6-dihydro-5-azacytidine, did not induce HPRT expression. The inactive X chromosome present in the hybrid, was found to be late replicating, and experiments with synchronized cells showed that the induction of HPRT expression by 5-aza-2'-deoxycytidine occurred maximally in cells treated in the latter half of the S phase. Two division cycles were required after analog treatment for the highest frequency of expression of the induced gene. Because these analogs are powerful inhibitors of the methylation of cytosine residues in DNA, the results imply that demethylation of specific DNA sequences may be required for the reexpression of human HPRT. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 79 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1982-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Azacitidine Analogs & Derivatives Genes Hypoxanthine Phosphoribosyltransferase Genetics Interphase Sex Chromosomes Physiology X Chromosome Animals Pharmacology Cell Division DNA Metabolism Hybrid Cells Methylation Mice Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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