Mechanism of stimulation of murine type-C RNA tumor virus production by glucocorticoids: post-transcriptional effects.
We have previously shown that dexamethasone stimulates production of type-C virus from seemingly normal murine fibroblasts (BALB/3T3) and from transformed (Kirsten sarcoma-leukemia virus) nonproducing cells (BALB/K3T3) induced by 5-iododeoxyuridine. In this report, we further examine the mechanism of this effect by using BALB/K3T3 cells. Several observations suggest that this effect is post-transcriptional. The optimal stimulation by dexamethasone is obtained when dexamethasone is given 24 to 48 h after 5-iododeoxyuridine induction. Although this effect is late, time course experiments suggest that dexamethasone does not act to promote release of preformed virions. The stimulation by dexamethasone is blocked when cells are treated with cordycepin (3'-deoxyadenosine) during the first 24 h of induction, but not when cordycepin is added later. Conversely, interferon, which inhibits virus production, interferes with dexamethasone when it is added late or after removal of the steroid. The results of molecular hybridization experiments show that there is no detectable increase in Kirsten sarcoma-leukemia virus-specific RNA in dexamethasone-treated cells (with or without 5-iododeoxyuridine). The results of the time course studies, and the cordycepin, interferon, and hybridization experiments, suggest that the effect of dexamethasone on type-C virus production in this system is post-transcriptional.
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004279:DNA, Viral; D003839:Deoxyadenosines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D017988:Gammaretrovirus / Q000032:analysis / Q000254:growth & development*; D007065:Idoxuridine / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D009693:Nucleic Acid Hybridization; D012367:RNA, Viral / Q000032:analysis; D012190:Retroviridae / Q000254:growth & development*; D013268:Stimulation, Chemical; D013997:Time Factors; D014158:Transcription, Genetic; D014316:Tritium; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D003839:Deoxyadenosines; D012367:RNA, Viral; D014316:Tritium; D003907:Dexamethasone; D007372:Interferons; D007065:Idoxuridine