title: Transcriptional activation of endogenous rat retrovirus with and without hypomethylation of proviral DNA.
abstract: Induction of latent, endogenous retrovirus from normal vertebrate cells has been reported following exposure in-vitro to the thymidine analog 5-bromodeoxyuridine (BrdU), as well as to the cytidine analog 5-azacytidine (azaC). Although the mode of action of BrdU is still unclear, azaC is known to cause the hypomethylation of DNA in replicating cells. This work was performed in order to determine whether a common molecular mechanism existed. Although both drugs were equally effective in the induction of the same proviral DNA in normal rat embryo cells, only azaC-treated sequences demonstrated extensive hypomethylation of proviral genes. In contrast, viral-specific sequences from BrdU-treated DNA were indistinguishable from untreated samples with respect to digestion with Hpa II and Msp I. It is likely, therefore, that the drugs effect viral induction by different mechanisms, and that hypomethylation of structural genes may not be a requisite for transcriptional activation in general of proviral DNA.
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism*; D005347:Fibroblasts; D005786:Gene Expression Regulation; D008745:Methylation; D051381:Rats; D012190:Retroviridae / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014775:Virus Activation / Q000187:drug effects*; D014776:Virus Cultivation
chemical_list: D004279:DNA, Viral; D001973:Bromodeoxyuridine; D001374:Azacitidine