Early modifications of nucleic acid metabolism and nuclear lipid biosynthesis associated with antiproliferative activity of interferon-alpha on Daudi lymphoma cells.
The effect of human recombinant DNA interferon-alpha type A (rIFN alpha A) on nuclear lipid biosynthesis and on in vitro nucleic acid synthesis was investigated in Daudi lymphoma cells sensitive (Daudi Is) or resistant (Daudi Ir) to the antiproliferative activity of this glycoprotein. In the Daudi Is studied at 90 min and up to 8 h, relative proportions of 3H-labeled nuclear lipids were reproducibly altered as compared to controls: phosphatidylcholine increased while phosphatidylserine and total neutral lipids decreased. These changes were not detected in parallel studies of the whole cell extracts. No significant changes in the profiles of nuclear lipids were observed in Daudi Ir. Decreased rates of alpha DNA polymerase and of RNA transcription were evident within 90 min in the Daudi Is nuclei but not in untreated controls or nuclei from rIFN alpha A-treated Daudi Ir cells, thus suggesting a possible relationship of the rapid alterations of nuclear lipid biosynthesis in Daudi Is cells to the rIFN alpha A antiproliferative activity.
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Istituto di Morfologia Umana Normale, Università di Chieti, Italy.
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Grimley
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D002051:Burkitt Lymphoma; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis* / Q000302:isolation & purification; D010743:Phospholipids / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D011994:Recombinant Proteins; D013942:Thymine Nucleotides / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000378:metabolism
D004273:DNA, Neoplasm; D007370:Interferon Type I; D008055:Lipids; D010743:Phospholipids; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D013942:Thymine Nucleotides; D005990:Glycerol; C024157:thymidine 5'-triphosphate; D014544:Uridine Triphosphate