Inhibitory effect of prostaglandin D2 on DNA synthesis in nuclei.
Prostaglandin (PG) D2 treatment inhibited DNA synthesis in isolated nuclei of mastocytoma P-815, 2-E-6 cells. On treatment with PGD2 (10 micrograms/ml), the inhibition was distinct by 8 hrs, and complete after 18 hrs. This effect of PGD2 on DNA synthesis in nuclei was not direct or mediated by cyclic AMP, but was a cell-mediated reaction. The cytoplasmic fractions of PGD2-treated and untreated cells both had stimulatory effects and their potencies were the same except for that of the cytoplasmic fraction of 8 hr-treated cells, which was less than that of the cytoplasmic fraction of untreated cells. On treatment with PGD2, inhibition of DNA synthesis in the nuclei began after 8 hrs, and this inhibition could not be reversed, even by adding the cytoplasmic fraction from untreated cells to the assay system. A nuclear salt extract prepared by adding 0.3 M NaCl to nuclei of cells that had been treated with PGD2 for 18 hrs had a much smaller stimulatory effect on DNA synthesis of salt-treated nuclei than an extract of nuclei from untreated cells. It is suggested that inhibition of cell growth by PGD2 is not mediated by intracellular cyclic AMP, but that PGD2 induces a factor(s) that inhibits nuclear DNA synthesis.
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005260:Female; D012515:Mast-Cell Sarcoma / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D004273:DNA, Neoplasm; D011457:Prostaglandins D; D005576:Colforsin; D012965:Sodium Chloride; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015230:Prostaglandin D2