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 f ollowing a 3-h exposure to nontoxic or toxic doses of ametantrone (AMT ), poly(adenylate-uridylate) (polyr(A-U), or an AMT/polyr(A-U) combina tion, While distribution of nucleic acids within the various nucleolar components is not modified following all treatments, the nucleoli exh ibit 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 A MT/polyr(A-U) > AMT approximate to polyr(A-U) > sham-treated, while th e 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 interca late into DNA and inhibit rDNA transcription as well as rRNA processin g and release of nascent preribosomes from the nucleolus. (C) 1997 Aca demic Press.