| Abstract | Effective treatment of certain cancers with 5-fluorouracil (5-FU) and irradiation is well established; however, the most effective combination of these agents remains controversial. Although 5-FU has been identified as a radiosensitizer, the mechanism of action remains unknown. To assess the effect of combination, 5-FU and ultraviolet (UV), we constructed a new in vitro model with MCF-7 human breast cancer cells that measures growth inhibition and morphologic changes in nuclear argyrophilic nucleolar organizer regions (AgNORs). Cells were incubated in media containing 0, 50, 100 and 500 ng/ml 5-FU for 48 h, they were also exposed to UV irradiation of 90 J/m(2) at the beginning, middle, or end of the incubation period. The cells were incubated for an additional 48 h with 5-FU free media. A combined treatment with 5-FU and UV radiation demonstrated an additive inhibitory effect. The strongest growth inhibition was observed when UV exposure was at the beginning of the 5-FU treatment at 5-FU concentrations of 100 and 500 ng/ml. To elucidate the activity of 5-FU radiosensitization, we investigated the aggregation Pof AgNOR, which we previously established to reflect rRNA inhibition. A combined treatment with 5-FU and UV radiation accelerated the rate of AgNOR aggregation at 5-FU concentrations of 50 and 100 ng/ml. The timing of UV irradiation did not affect the rate of AgNOR aggregation. A combined treatment with 5-FU and UV radiation showed an additive inhibitory effect on MCF-7 cell growth that might be explained, in part, by rRNA inhibition. |
| Authors | T Hamaoka, Y Furuya, K Yamamoto, Y Kuroda
(Affiliation: First Department of Surgery, Kobe University School of Medicine, Kusunoki-chou 7-5-1, Chuo-ku, Kobe, Japan. qze16435 at nifty.ne.jp)
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| Journal | Cancer letters
(Cancer Lett)
Vol. 154
Issue 2
Pg. 183-7
(Jun 30 2000)
ISSN: 0304-3835 IRELAND |
| PMID | 10806306
(Publication Type: Journal Article)
|
| Chemical References |
- 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium
- Antimetabolites, Antineoplastic
- RNA, Ribosomal
- Tetrazolium Salts
- Fluorouracil
|
| Topics |
- Antimetabolites, Antineoplastic
(pharmacology)
- Breast Neoplasms
(drug therapy, radiotherapy)
- Cell Division
(drug effects, radiation effects)
- Cell Nucleus
(drug effects, radiation effects)
- Combined Modality Therapy
(methods)
- Dose-Response Relationship, Drug
- Fluorouracil
(pharmacology)
- Humans
- Nucleolus Organizer Region
(metabolism)
- RNA, Ribosomal
(metabolism)
- Tetrazolium Salts
(metabolism)
- Time Factors
- Tumor Cells, Cultured
- Ultraviolet Therapy
|
