MCF-7 growth inhibition by ultraviolet radiation and 5-fluorouracil: the importance of treatment sequence.

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
• Journal: Cancer letters (Cancer Lett) Vol. 154 Issue 2 Pg. 183-7 (Jun 30 2000) ISSN: 0304-3835 [Print] 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