Ultrastructural nucleolar alterations induced by an ametantrone/polyr(A-U) complex.
In the present study we examined the ultrastructural modifications as well as the precise distribution of DNA and RNA in RT4 cell nucleoli following a 3-h exposure to nontoxic or toxic doses of ametantrone (AMT), poly(adenylate-uridylate) (polyr(A-U), or an AMT/polyr(A-U) combination. While distribution of nucleic acids within the various nucleolar components is not modified following all treatments, the nucleoli exhibit several ultrastructural changes: redistribution of the nucleolar components, decrease in the number of fibrillar centers, and increase in the size of the fibrillar centers. The relative frequencies of the test agents to induce the apparition of nucleoli of compact type are AMT/polyr(A-U) > AMT approximately polyr(A-U) > sham-treated, while the abilities of the test agents to induce the nucleolar segregation are AMT/polyr(A-U) approximately AMT > polyr(A-U) > sham-treated cells. These ultrastructural changes are characteristics of drugs that intercalate into DNA and inhibit rDNA transcription as well as rRNA processing and release of nascent preribosomes from the nucleolus.
Thiry
M
M
Laboratory of Cell and Tissue Biology, University of Liège, Belgium. mthiry@ulg.ac.be
Jamison
J M
JM
Gilloteaux
J
J
Summers
J L
JL
Goessens
G
G
D000970:Antineoplastic Agents / Q000633:toxicity*; D002466:Cell Nucleolus / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D007369:Interferon Inducers / Q000633:toxicity*; D008854:Microscopy, Electron; D008942:Mitoxantrone / Q000031:analogs & derivatives* / Q000633:toxicity; D009696:Nucleic Acids / Q000032:analysis; D011063:Poly A-U / Q000633:toxicity*; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure; D001749:Urinary Bladder Neoplasms
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007369:Interferon Inducers; D009696:Nucleic Acids; D012334:RNA, Neoplasm; D011063:Poly A-U; D008942:Mitoxantrone; C020182:ametantrone