The Generation and Characterization of a Radiation-Resistant Model System to Study Radioresistance in Human Breast Cancer Cells

Pearce, A. G., Segura, T. M., Rintala, A. C., Rintala-Maki, N. D. and Lee, H. The Generation and Characterization of a Radiation-Resistant Model System to Study Radioresistance in Human Breast Cancer Cells. Radiat. Res. 156, 739–750 (2001). To systematically study the selection of radioresistant cel...

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Veröffentlicht in:Radiation research 2001-12, Vol.156 (6), p.739-750
Hauptverfasser: Pearce, Andrew G., Segura, Tamika M., Rintala, Anne C., Rintala-Maki, Nina D., Lee, Hoyun
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container_end_page 750
container_issue 6
container_start_page 739
container_title Radiation research
container_volume 156
creator Pearce, Andrew G.
Segura, Tamika M.
Rintala, Anne C.
Rintala-Maki, Nina D.
Lee, Hoyun
description Pearce, A. G., Segura, T. M., Rintala, A. C., Rintala-Maki, N. D. and Lee, H. The Generation and Characterization of a Radiation-Resistant Model System to Study Radioresistance in Human Breast Cancer Cells. Radiat. Res. 156, 739–750 (2001). To systematically study the selection of radioresistant cells in clinically advanced breast cancer, a model system was generated by treating MDA-MB231 breast cancer cells with fractionated γ radiation. A clonogenic assay of the surviving cell populations showed that 2–6 Gy per fraction resulted in a rapid selection of radioresistant populations, within three to five fractions. Irradiation with additional fractions after this initial increase did not increase the radioresistance of the surviving population significantly. Doses of 0.5 and 8 Gy per fraction were not effective in selecting radioresistant cells. To further determine the cause of the changes in radiosensitivity, 15 clones were isolated from the cell populations treated with 40 or 60 Gy with 2 or 4 Gy per fraction, respectively, and were analyzed for radiosensitivity. The average D10 for these clones was 6.75 ± 0.36 Gy, which was higher than that for the parental cell population (D10 = 6.0 ± 0.2 Gy). The operation of cell cycle checkpoints and the doubling time were similar for both the nonirradiated parental population and the isolated radioresistant subclones. In contrast, a decrease in the apoptotic potential was correlated (r = 0.7, P < 0.01) with increased survival after irradiation, suggesting that apoptosis is an important factor in determining radioresistance under our experimental conditions. We also isolated several subclones from the nonirradiated parental cell population and analyzed them to determine their radiosensitivity after fractionated irradiation. Ten fractions of 4 Gy (40 Gy in total) did not result in a significant increase in the radioresistance of these subclones compared to the irradiated cell populations. The possible mechanisms of the increased radioresistance after fractionated irradiation are discussed.
doi_str_mv 10.1667/0033-7587(2001)156[0739:TGACOA]2.0.CO;2
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To further determine the cause of the changes in radiosensitivity, 15 clones were isolated from the cell populations treated with 40 or 60 Gy with 2 or 4 Gy per fraction, respectively, and were analyzed for radiosensitivity. The average D10 for these clones was 6.75 ± 0.36 Gy, which was higher than that for the parental cell population (D10 = 6.0 ± 0.2 Gy). The operation of cell cycle checkpoints and the doubling time were similar for both the nonirradiated parental population and the isolated radioresistant subclones. In contrast, a decrease in the apoptotic potential was correlated (r = 0.7, P &lt; 0.01) with increased survival after irradiation, suggesting that apoptosis is an important factor in determining radioresistance under our experimental conditions. We also isolated several subclones from the nonirradiated parental cell population and analyzed them to determine their radiosensitivity after fractionated irradiation. 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G., Segura, T. M., Rintala, A. C., Rintala-Maki, N. D. and Lee, H. The Generation and Characterization of a Radiation-Resistant Model System to Study Radioresistance in Human Breast Cancer Cells. Radiat. Res. 156, 739–750 (2001). To systematically study the selection of radioresistant cells in clinically advanced breast cancer, a model system was generated by treating MDA-MB231 breast cancer cells with fractionated γ radiation. A clonogenic assay of the surviving cell populations showed that 2–6 Gy per fraction resulted in a rapid selection of radioresistant populations, within three to five fractions. Irradiation with additional fractions after this initial increase did not increase the radioresistance of the surviving population significantly. Doses of 0.5 and 8 Gy per fraction were not effective in selecting radioresistant cells. 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Mammary gland</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Irradiation</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Radiation dosage</topic><topic>Radiation Tolerance</topic><topic>Radiotherapy</topic><topic>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. 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G., Segura, T. M., Rintala, A. C., Rintala-Maki, N. D. and Lee, H. The Generation and Characterization of a Radiation-Resistant Model System to Study Radioresistance in Human Breast Cancer Cells. Radiat. Res. 156, 739–750 (2001). To systematically study the selection of radioresistant cells in clinically advanced breast cancer, a model system was generated by treating MDA-MB231 breast cancer cells with fractionated γ radiation. A clonogenic assay of the surviving cell populations showed that 2–6 Gy per fraction resulted in a rapid selection of radioresistant populations, within three to five fractions. Irradiation with additional fractions after this initial increase did not increase the radioresistance of the surviving population significantly. Doses of 0.5 and 8 Gy per fraction were not effective in selecting radioresistant cells. To further determine the cause of the changes in radiosensitivity, 15 clones were isolated from the cell populations treated with 40 or 60 Gy with 2 or 4 Gy per fraction, respectively, and were analyzed for radiosensitivity. The average D10 for these clones was 6.75 ± 0.36 Gy, which was higher than that for the parental cell population (D10 = 6.0 ± 0.2 Gy). The operation of cell cycle checkpoints and the doubling time were similar for both the nonirradiated parental population and the isolated radioresistant subclones. In contrast, a decrease in the apoptotic potential was correlated (r = 0.7, P &lt; 0.01) with increased survival after irradiation, suggesting that apoptosis is an important factor in determining radioresistance under our experimental conditions. We also isolated several subclones from the nonirradiated parental cell population and analyzed them to determine their radiosensitivity after fractionated irradiation. Ten fractions of 4 Gy (40 Gy in total) did not result in a significant increase in the radioresistance of these subclones compared to the irradiated cell populations. The possible mechanisms of the increased radioresistance after fractionated irradiation are discussed.</abstract><cop>Oak Brook, Il</cop><pub>Radiation Research Society</pub><pmid>11741498</pmid><doi>10.1667/0033-7587(2001)156[0739:TGACOA]2.0.CO;2</doi><tpages>12</tpages></addata></record>
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source Jstor Complete Legacy; MEDLINE; BioOne Complete
subjects Apoptosis
Biological and medical sciences
Breast Neoplasms - pathology
Cell cycle
Cell lines
Cell membranes
Cells
Dose Fractionation
Genital system. Mammary gland
Gynecology. Andrology. Obstetrics
Humans
Irradiation
Mammary gland diseases
Medical sciences
Radiation dosage
Radiation Tolerance
Radiotherapy
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
REGULAR ARTICLES
Space life sciences
Tumor Cells, Cultured
Tumors
title The Generation and Characterization of a Radiation-Resistant Model System to Study Radioresistance in Human Breast Cancer Cells
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