Ultrastructural nucleolar alterations induced by an ametantrone–poly r(A-U) complex.
Antineoplastic Agents/*pharmacology; Carcinoma; Cell Nucleolus/*chemistry/drug effects/ultrastructure; Cultured/chemistry/drug effects/ultrastructure; DNA; Humans; Immunoelectron; Microscopy; Mitoxantrone/*analogs & derivatives/pharmacology; Neoplasm/*analysis; Neoplasm/analysis; Poly A-U/*pharmacology; Ribosomal/analysis; Ribosomal/analysis/ultrastructure; RNA; Transitional Cell; Tumor Cells; Urinary Bladder Neoplasms
The current study has documented changes in the ultrastructure as well as in the intranucleolar distribution of rDNA and rRNA in RT4 (human transitional cell bladder carcinoma) cell nucleoli following a 3-h exposure to toxic doses of 50 microM ametantrone (AMT), 200 microM poly (adenylate-uridylate) (poly r(A-U) or an AMT/poly r(A-U) combination with an AMT/polyribonucleotide ratio of 1:4 and a poly r(A-U) concentration of 200 microM. While the main nucleolar components (fibrillar center (F), dense fibrillar component (D), granular component (G) and interstices (I) can be discerned following all treatments, the nucleoli exhibit: compaction, segregation, a decrease in the number of F, an increase in the size of remaining F, margination of intranucleolar chromatin and retention of intranucleolar pre-rRNA and rRNA. The relative abilities of the test agents to induce nucleolar compaction are AMT/poly r(A-U) \textgreater poly r(A-U) \textgreater AMT \textgreater sham-treated, while the abilities of the test agents to induce the remaining nucleolar changes are AMT/poly r(A-U) \textgreater or = AMT \textgreater poly r(A-U) \textgreater sham-treated cells. Poly r(A-U) and the induced interferon induce nucleolar compaction, while AMT produces nucleolar segregation. These results are consistent with a model in which the poly r(A-U) and/or the AMT inhibit DNA transcription and rRNA processing as well as the release of nascent preribosomes from the nucleolus.
Jamison J M; Gilloteaux J; Thiry M; Authelet M; Goessens G; Summers J L
Tissue & cell
1998
1998-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0040-8166(98)80061-x" target="_blank" rel="noreferrer noopener">10.1016/s0040-8166(98)80061-x</a>
Ultrastructural nucleolar alterations induced by an ametantrone/polyr(A-U) complex
actinomycin-d; Cell Biology; cells; fibrillar centers; human interferon; invitro antiviral activity; mitoxantrone; novatrone; nucleic-acids; Oncology; photodynamic therapy; poly r(a-u); rna-synthesis
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 approximate to polyr(A-U) > sham-treated, while the abilities of the test agents to induce the nucleolar segregation are AMT/polyr(A-U) approximate to AMT > polyr(A-U) > sham-treated cells, These ultrastructural changes are characteristic of drugs that intercalate into DNA and inhibit rDNA transcription as well as rRNA processing and release of nascent preribosomes from the nucleolus. (C) 1997 Academic Press.
Thiry M; Jamison J M; Gilloteaux J; Summers J L; Goessens G
Experimental Cell Research
1997
1997-10
Journal Article
<a href="http://doi.org/10.1006/excr.1997.3743" target="_blank" rel="noreferrer noopener">10.1006/excr.1997.3743</a>
Ultrastructural Nucleolar Alterations Induced By An Ametantrone Poly R(a-u) Complex In A Human Bladder Cancer
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Gilloteaux J; Jamison J M; Thiry M; Goessens G; Summers J L
Faseb Journal
1997
1997-02
Journal Article or Conference Abstract Publication
n/a