Bleomycin differentially inhibits picornavirus, herpesvirus and poxvirus replication in a human carcinoma cell line.
MS-757, a cervix carcinoma cell line, was exposed to bleomycin at concentrations up to 200 microM for periods of 1 to 24 hours. Bleomycin treatment caused the level of DNA synthesis in uninfected cells to drop to 13% of the level achieved in the controls. Protein synthesis fell to 50%, but RNA synthesis was not affected. Exposure of uninfected cells to 200 microM bleomycin for 24 h did not induce significant cell death measured as permeability to Trypan Blue). A tetrazolium dye-reduction assay, however, showed that cell viability measured as mitochondrial activity was reduced by 50%. In contrast, the clonogenicity of the treated cells (measured as colony-forming ability) fell to less than 1% of the level in untreated controls. Bleomycin effected a highly selective inhibition of virus replication measured as production of infectious progeny virus. The replication of the RNA virus, coxsackievirus B5, was largely unaffected by bleomycin, whereas the replication of the DNA virus, herpes simplex virus type 2, was inhibited to the same extent as cellular DNA synthesis. In contrast, bleomycin caused a 2 to 3 log10-fold suppression of the production of progeny virus after infection with the DNA virus, vaccinia virus. When an early gene product (expressed prior to virus DNA replication) of vaccinia virus was assayed, little inhibitory effect of bleomycin could be demonstrated, indicating that the early transcription and translation of vaccinia virus was only modestly influenced by bleomycin. The results argue against a DNA-based replication as the bleomycin-susceptible function independent of genome, replication enzymes, and site of synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Nørskov-Lauritsen
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N
Department of Virus and Cancer, Danish Cancer Society, Arhus C.
Ebbesen
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P
D000998:Antiviral Agents / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000502:physiology; D005260:Female; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms; D014616:Vaccinia virus / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D001761:Bleomycin