ULTRASTRUCTURAL NUCLEOLAR ALTERATIONS INDUCED BY AN AMETANTRONE - POLY R(A-U) COMPLEX

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 exp osure to toxic doses of 50 mu M ametantrone (AMT), 200 mu M poly (aden ylate-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 mu M. While the main nucleolar components (fibrillar center (F ), dense fibrillar component (D), granular component (G) and interstic es (I)) can be discerned following all treatments, the nucleoli exhibi t: compaction, segregation, a decrease in the number of F, an increase in the size of remaining F, margination of intranucleolar chromatin a nd retention of intranucleolar pre-rRNA and rRNA, The relative abiliti es of the test agents to induce nucleolar compaction are AMT/poly r(A- U) > poly r(A-U) > AMT > sham-treated, while the abilities of the test agents to induce the remaining nucleolar changes are AMT/poly r(A-U) greater than or equal to AMT > poly r(A-U) > sham-treated cells. Poly r(A-U) and the induced interferon induce nucleolar compaction, while A MT produces nucleolar segregation. These results are consistent with a model in which the poly r(A-U) and/or the AMT inhibit DNA transcripti on and rRNA processing as well as the release of nascent preribosomes from the nucleolus.