title: Dimethyl sulfoxide inhibits the expression of early growth-response genes and arrests fibroblasts at quiescence.
abstract: We have previously shown that dimethyl sulfoxide (DMSO) treatment of mouse embryo fibroblasts (MEF) at the early hours of mitogenic stimuli resulted in the inhibition of DNA and protein synthesis; delayed treatment of serum-stimulated cells with DMSO had little effect on the synthesis of these macromolecules. Here, we demonstrate the specific inhibition of expression of early growth response genes by DMSO in serum-stimulated MEF. The expression of interleukin 6, and of oncogenes c-myc and c-fos were inhibited when the cells were treated with 2% DMSO from the beginning of serum-stimulated growth but not after 3 h of mitogenic stimuli. Although the actin gene is an early serum-response gene, its expression was not affected by DMSO. The synthesis of another serum-induced protein, the plasminogen activator inhibitor-1 was blocked during concurrent and delayed (after 3 h of stimulation) treatment of serum-stimulated fibroblasts with DMSO. The expression of glyceraldehyde-3-phosphate dehydrogenase gene was not affected by DMSO. These results indicate that the expression of non-growth-related genes are either not affected or affected nonspecifically both at early and late stages of serum-induced growth of mouse embryo fibroblasts. The serum-induced expression of c-fos gene was abolished by DMSO treatment of MEF while the phorbol 12-myristate 13-acetate-induced expression of fos gene was not, indicating that the PMA signaling pathway was refractory to DMSO. Treatment of cells with medium containing 2% DMSO for 24-48 h prevents them from progression into cell cycle by preventing the expression of genes involved in G0-G1 transition of quiescent cells.
authors.affiliation: Cancer Biology Division, School of Biological Sciences, Madurai Kamaraj University, India.
authors.forename: S
authors.initials: S
authors.lastname: Srinivas
authors.forename: T A
authors.initials: TA
authors.lastname: Sironmani
authors.forename: G
authors.initials: G
authors.lastname: Shanmugam
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D015342:DNA Probes; D004261:DNA Replication / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics* / Q000302:isolation & purification; D007700:Kinetics; D051379:Mice; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
chemical_list: D000199:Actins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide