Cytochemical and autoradiographic study of the early nuclear lesions induced by an ellipticine derivative in isolated rat hepatocytes.
Isolated rat liver cells maintained in primary culture were treated with 9-OH ellipticinium (9-OH E+). The effects of this drug on the nuclear ultrastructure and on the chromatin transcriptional activity were studied by the combination of cytochemistry with hgih resolution autoradiography. At a low concentration (1 microgram/ml) for periods ranging from 10 min to 3 hr, 9-OH E+ induced chromatin clumping, nucleolar microsegregation and a diminution in the number of perichromatin and interchromatin fibrils. Autoradiography revealed that this compound inhibited rapidly the incorporation of [5-3H]-uridine in the nucleus, preferentially but not exclusively in the nucleolar area. In addition, the distribution of the radioactivity in the nucleoli proved that the processing of the pre-ribosomal ribonucleic acids (pre-rRNA) synthesized in the presence of the drug was blocked while the processing during 9-OH E+ treatment of normally synthesized pre-rRNA was not altered. These findings suggest that the inhibition of pre-rRNA processing might result from an impairment of factors controlling this processing rather than from a direct action of 9-OH E+ on pre-rRNA molecules.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001345:Autoradiography; D002466:Cell Nucleolus / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002843:Chromatin / Q000187:drug effects; D004611:Ellipticines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D014529:Uridine / Q000378:metabolism
D000470:Alkaloids; D000970:Antineoplastic Agents; D002843:Chromatin; D004611:Ellipticines; C008009:9-hydroxyellipticine; D014529:Uridine