Comparison of the effectiveness of S phase inhibitors in altering gene expression.
Evidence suggests that an unidentified mechanism associated with the S phase inhibition properties of 5-azacytidine may be just as or more important than its hypomethylating properties in eliciting gene expression. To determine how important the S phase properties of this agent are to the alteration of gene expression, I compared it with other S phase inhibitors which do not affect DNA methylation for their ability to derepress the hypoxanthine phosphoribosyl transferase gene on the inactive X chromosome. Of these agents, only 5-azacytidine was able to derepress this gene in CAK cells. It appears that 5-azacytidine does alter gene expression via DNA hypomethylation. The ability of other S phase inhibitors to increase fetal globin expression may be peculiar to this genetic system.
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D005260:Female; D005796:Genes / Q000187:drug effects*; D006918:Hydroxyurea / Q000494:pharmacology*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007399:Interphase / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D013936:Thymidine / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014960:X Chromosome / Q000187:drug effects
D003561:Cytarabine; D007041:Hypoxanthine Phosphoribosyltransferase; D001374:Azacitidine; D013936:Thymidine; D006918:Hydroxyurea