A Nitroimidazole Derivative, PR-350, Enhances the Killing of Pancreatic Cancer Cells Exposed to High-dose Irradiation under Hypoxia

The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gammaray irradiation in vitro. The percentages of dead cells were analyzed with a multiwell plate reader to measure the fluore...

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Bibliographic Details
Published in:JOURNAL OF RADIATION RESEARCH 2002, Vol.43 (1), p.43-51
Main Authors: Mizumoto, Kazuhiro, Qian, Li-Wu, Zhang, Li, Nagai, Eishi, Kura, Shinobu, Tanaka, Masao
Format: Article
Language:English
Subjects:
Cancer cells
Cell death
Cell Death - drug effects
Cell Death - radiation effects
Cell Hypoxia
DNA, Neoplasm - drug effects
DNA, Neoplasm - radiation effects
Humans
Imidazoles - pharmacology
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - radiotherapy
Public relations
Radiation Tolerance
Radiation-Sensitizing Agents - pharmacology
Tumor Cells, Cultured
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Summary:The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gammaray irradiation in vitro. The percentages of dead cells were analyzed with a multiwell plate reader to measure the fluorescence intensity of propidium iodide before and after a digitonin treatment. The sensitizing effect of PR-350 on cell killing by high-dose irradiation was confirmed by time-course, dose-dependency, and microscopic observations. In five of seven pancreatic cancer cell lines in which the number of dead cells was determined 5 days after 30 Gy irradiation in the presence of PR-350, the number was significantly increased under hypoxic conditions, but not under aerobic conditions. The selective radiosensitive effect of PR-350 on hypoxic cells was also confirmed by flow cytometry. The results indicate that PR-350 can enhance the killing of pancreatic cancer cells by high-dose irradiation under hypoxia, which supports its clinical radiosensitizing effects when administered during intraoperative irradiation to pancreatic cancer.
ISSN:0449-3060
1349-9157
DOI:10.1269/jrr.43.43