Title aggregation patterns of argyrophilic nucleolar organizer regions induced by 5-fluorouracil in the nuclei of MCF-7 human breast cancer cells.
The effects of tamoxifen and 5-fluorouracil (5-FU) on the patterns of argyrophilic nucleolar organizer regions (AgNORs) in MCF7 human breast cancer cells were studied. Tamoxifen and 5-FU both inhibited the growth of MCF-7 cells by 18% by day 3 of culture, but each had different effects on the AgNORs. Whereas no significant changes were induced by tamoxifen, effects on the AgNORs of MCF-7 cells by 5-FU were dramatic: 5-FU treatment changed the pattern of AgNORs, reducing the number of satellites by aggregation, typically to a single aggregation around nucleoli in a sphenoidal fashion. We named these morphological changes: fluorouracil induced AgNOR aggregations (FAA). Following treatment with 500 ng/ml 5-FU, FAA developed rapidly. AgNORs forming two or three aggregates in 24% (6 h), 24% (12 h), 40% (24 h) and 34% (48 h) of cells, compared to a control rate of 14%. Single large aggregate was rarely found in untreated cultures but after 6, 12, 24 and 48 h treatment with 500 ng/ml 5-FU, AgNORs had formed a single aggregate in 6, 8, 16 and 22% of cells, respectively. FAA were observed at a concentration of 100 ng/ml 5-FU; 48 h treatment resulted in cells in which two or three aggregates were increased by 24% and single aggregate by 16%. These large single aggregates were larger than nucleoli stained by Papanicolau staining.
Nishihara
T
T
The First Department of Surgery, Kobe University School of Medicine, Japan.
Furuya
Y
Y
Yamamoto
K
K
Saitoh
Y
Y
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure*; D002449:Cell Aggregation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D003470:Culture Media; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure*; D009697:Nucleolus Organizer Region / Q000187:drug effects*; D016622:Silver Staining; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D003470:Culture Media; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D005472:Fluorouracil